C. Verellen-Dumoulin - Academia.edu (original) (raw)
Papers by C. Verellen-Dumoulin
Bulletin Et Memoires De L Academie Royale De Medecine De Belgique, 2000
Le cancer colorectal est la deuxieme cause de mortalite en Europe occidentale. Notre lecture a po... more Le cancer colorectal est la deuxieme cause de mortalite en Europe occidentale. Notre lecture a pour but de decrire les progres genetiques recents et leur implication dans les mecanismes de la carcinogenese colorectale, ainsi que leurs consequences dans la prise en charge therapeutique et dans les mesures de prevention du cancer colorectal hereditaire non polyposique, ou syndrome HNPCC. L'histoire familiale et les signes cliniques, coliques et extracoliques, qui permettent de suspecter ce syndrome autosomique dominant, sont presentes (criteres d'Amsterdam revus, et ceux de Bethesda). Les six principaux genes MLH1, MSH2, MSH6, PMS2, PMS3 et MSH3, responsables du syndrome HNPCC, sont directement impliques dans le systeme de reparation des mesappariements des bases nucleotidiques, lors de la replication de l'ADN a chaque cycle cellulaire. Un defaut constitutif d'un de ces genes, suivi de la perte de fonction de l'allele homologue, est responsable du phenotype mutateur des tumeurs, qui se manifeste par des variations de taille de sequences repetitives que sont les microsatellites, et par une perte d'expression de proteine specifique au gene implique. Afin de donner une information precise aux cliniciens et aux patients concernes, et en l'absence de criteres absolus de diagnostic du syndrome HNPCC, nous avons developpe, depuis septembre 1998, une strategie de diagnostic genetique du syndrome et de recherche de la mutation responsable pour les deux principaux genes MLH1 et MSH2. Pour les patients, le diagnostic genetique pourrait modifier la prise en charge chirurgicale et le traitement medical, et dans les familles a risque, le diagnostic genetique predictif devrait contribuer tres positivement a la prevention du cancer ».
PloS one, 2018
Surveillance of congenital anomalies is important to identify potential teratogens. This study an... more Surveillance of congenital anomalies is important to identify potential teratogens. This study analysed the prevalence of 61 congenital anomaly subgroups (excluding chromosomal) in 25 population-based EUROCAT registries (1980-2012). Live births, fetal deaths and terminations of pregnancy for fetal anomaly were analysed with multilevel random-effects Poisson regression models. Seventeen anomaly subgroups had statistically significant trends from 2003-2012; 12 increasing and 5 decreasing. The annual increasing prevalence of severe congenital heart defects, single ventricle, atrioventricular septal defects and tetralogy of Fallot of 1.4% (95% CI: 0.7% to 2.0%), 4.6% (1.0% to 8.2%), 3.4% (1.3% to 5.5%) and 4.1% (2.4% to 5.7%) respectively may reflect increases in maternal obesity and diabetes (known risk factors). The increased prevalence of cystic adenomatous malformation of the lung [6.5% (3.5% to 9.4%)] and decreased prevalence of limb reduction defects [-2.8% (-4.2% to -1.5%)] are u...
European Journal of Human Genetics, 2014
Meckel-Gruber Syndrome is a rare autosomal recessive lethal ciliopathy characterized by the triad... more Meckel-Gruber Syndrome is a rare autosomal recessive lethal ciliopathy characterized by the triad of cystic renal dysplasia, occipital encephalocele and postaxial polydactyly. We present the largest population-based epidemiological study to date using data provided by the European Surveillance of Congenital Anomalies (EUROCAT) network. The study population consisted of 191 cases of MKS identified between January 1990 and December 2011 in 34 European registries. The mean prevalence was 2.6 per 100 000 births in a subset of registries with good ascertainment. The prevalence was stable over time, but regional differences were observed. There were 145 (75.9%) terminations of pregnancy after prenatal diagnosis, 13 (6.8%) fetal deaths, 33 (17.3%) live births. In addition to cystic kidneys (97.7%), encephalocele (83.8%) and polydactyly (87.3%), frequent features include other central nervous system anomalies (51.4%), fibrotic/cystic changes of the liver (65.5% of cases with post mortem examination) and orofacial clefts (31.8%). Various other anomalies were present in 64 (37%) patients. As nowadays most patients are detected very early in pregnancy when liver or kidney changes may not yet be developed or may be difficult to assess, none of the anomalies should be considered obligatory for the diagnosis. Most cases (90.2%) are diagnosed prenatally at 14.3 ± 2.6 (range 11-36) gestational weeks and pregnancies are mainly terminated, reducing the number of LB to one-fifth of the total prevalence rate. Early diagnosis is important for timely counseling of affected couples regarding the option of pregnancy termination and prenatal genetic testing in future pregnancies.
The Journal of Rheumatology, 2011
Objective.To compare the distribution of congenital anomalies within the VACTERL association (ver... more Objective.To compare the distribution of congenital anomalies within the VACTERL association (vertebral defects, anal atresia, cardiac, tracheoesophageal, renal, and limb abnormalities) between patients exposed to tumor necrosis factor-α (TNF-α) antagonist and the general population.Methods.Analysis for comparison of proportional differences to a previous publication between anomaly subgroups, according to subgroup definitions of the European Surveillance of Congenital Anomalies (EUROCAT), a population-based database.Results.Most EUROCAT subgroups belonging to the VACTERL association contained only one or 2 records of TNF-α antagonist exposure, so comparison of proportions was imprecise. Only the category “limb abnormalities” showed a significantly higher proportion in the general population.Conclusion.The high number of congenital anomalies belonging to the VACTERL association from a report of pregnancies exposed to TNF-α antagonists could not be confirmed using a population-based ...
BMJ, 2016
ObjeCtives To provide contemporary estimates of the prevalence of microcephaly in Europe, determi... more ObjeCtives To provide contemporary estimates of the prevalence of microcephaly in Europe, determine if the diagnosis of microcephaly is consistent across Europe, and evaluate whether changes in prevalence would be detected using the current European surveillance performed by EUROCAT (the European Surveillance of Congenital Anomalies). Design Questionnaire and population based observational study. setting 24 EUROCAT registries covering 570 000 births annually in 15 countries. PartiCiPants Cases of microcephaly not associated with a genetic condition among live births, fetal deaths from 20 weeks' gestation, and terminations of pregnancy for fetal anomaly at any gestation. Main OutCOMe Measures Prevalence of microcephaly (1 Jan 2003-31 Dec 2012) analysed with random effects Poisson regression models to account for heterogeneity across registries. results 16 registries responded to the questionnaire, of which 44% (7/16) used the EUROCAT definition of microcephaly (a reduction in the size of the brain with a skull circumference more than 3 SD below the mean for sex, age, and ethnic origin), 19% (3/16) used a 2 SD cut off, 31% (5/16) were reliant on the criteria used by individual clinicians, and one changed criteria between 2003 and 2012. Prevalence of microcephaly in Europe was 1.53 (95% confidence interval 1.16 to 1.96) per 10 000 births, with registries varying from 0.4 (0.2 to 0.7) to 4.3 (3.6 to 5.0) per 10 000 (χ 2 =338, df=23, I 2 =93%). Registries with a 3 SD cut off reported a prevalence of 1.74 per 10 000 (0.86 to 2.93) compared with those with the less stringent 2 SD cut off of 1.21 per 10 000 (0.21 to 2.93). The prevalence of microcephaly would need to increase in one year by over 35% in Europe or by over 300% in a single registry to reach statistical significance (P<0.01). COnClusiOns EUROCAT could detect increases in the prevalence of microcephaly from the Zika virus of a similar magnitude to those observed in Brazil. Because of the rarity of microcephaly and discrepant diagnostic criteria, however, the smaller increases expected in Europe would probably not be detected. Clear diagnostic criteria for microcephaly must be adopted across Europe.
Annales de chirurgie de la main et du membre supérieur : organe officiel des sociétés de chirurgie de la main = Annals of hand and upper limb surgery, 1992
The trismus pseudocamptodactyly syndrome also called Hecht syndrome or Dutch-Kentucky syndrome is... more The trismus pseudocamptodactyly syndrome also called Hecht syndrome or Dutch-Kentucky syndrome is characterized by loss of the ability to fully open the mouth (trismus) and a finger contracture with progressive flexion of the fingers upon extension of the wrist (pseudocamptodactyly). Deformities of the foot may be associated e.g. hammer and claw toes, tightening of the muscles of the posterior part of the leg producing an equinovarus foot. The authors presents two affected individuals from one family from which nine members had some involvement. The expression of the syndrome may vary. The pattern of the finger contracture is specific. The inheritance is autosomal dominant.
Cancer Genetics and Cytogenetics, 2001
We report on three cases, two with myelodysplastic syndrome (MDS) and one with acute lymphoblasti... more We report on three cases, two with myelodysplastic syndrome (MDS) and one with acute lymphoblastic leukemia (ALL), displaying trisomy 16 as the sole cytogenetic anomaly. In none of these cases was a concomitant inv(16)(p13q22) detected by fluorescence in situ hybridization (FISH) or reverse transcription polymerase chain reaction (RT-PCR). Summarizing the literature, only six other cases cytogenetically characterized by an isolated trisomy 16 have been reported in hematological malignancies. These patients had either MDS, acute myeloblastic leukemia (AML), myelofibrosis, or ALL. All but one of these cases were aged less than 50.
Cancer Genetics and Cytogenetics, 2007
A retrospective cytogenetic study of acute myeloid leukemias (AML) and myelodysplastic syndromes ... more A retrospective cytogenetic study of acute myeloid leukemias (AML) and myelodysplastic syndromes (MDS) was conducted by the Groupe Francophone de Cytogénétique Hématologique (GFCH) to evaluate the structural abnormalities of chromosome 5 associated with other chromosomal abnormalities, in particular of chromosome 7, in these pathologies. In all, 110 cases of AML/MDS were recruited based on the presence of chromosome 5 abnormalities under conventional cytogenetics and supplemented by a systematic fluorescence in situ hybridization study of chromosomes 5 and 7. The abnormalities of the long arm of chromosome 5 (5q) were deletions of various sizes and sometimes cryptic. The 5q abnormalities were associated with translocations in 54% of cases and were simple deletions in 46%. In 68% of cases, 5q deletions were associated with chromosome 7 abnormalities, and 90% of these presented a complex karyotype. Of the 110 patients, 28 had a hematopoietic disorder secondary to chemotherapy, radiotherapy, or both. Among 82 patients with de novo AML/MDS, 63 were older than 60 years. Chromosomal abnormalities often associated hypodiploidy and chromosome 5 and 7 abnormalities in complex karyotypes, features resembling those of secondary hemopathies. Systematic investigation of the exposure to mutagens and oncogenes is thus essential to specify the factors potentially involved in MDS/AML with 5q abnormalities.
Birth Defects Research Part A: Clinical and Molecular Teratology, 2014
History and Funding Eurocat Northern Netherlands (NNL) started in 1981, and was a member of the E... more History and Funding Eurocat Northern Netherlands (NNL) started in 1981, and was a member of the EUROCAT network since that year. The registry is funded by the Dutch Ministry of Health, Welfare and Sports and is associated with the Department of Genetics of the University Medical Centre of Groningen. Population Coverage The registry is population-based, including babies born to all mothers resident in the registration area. In the beginning, the program covered 7,500 births annually in the province of Groningen and the northern part of the province of Drenthe. From 1989 onwards, coverage was gradually increased to 20,000 births annually in the provinces of Groningen, Friesland and Drenthe. In recent years the number of births in the region decreased to 18.500, approximately 10% of all births in the Netherlands. Home deliveries (25% of births per year) are included and it is estimated that only a few percent of resident mothers would give birth outside the defined registry area.
The American Journal of Human Genetics, 2000
Familial juvenile hyperuricemic nephropathy (FJHN), is an autosomal dominant renal disease charac... more Familial juvenile hyperuricemic nephropathy (FJHN), is an autosomal dominant renal disease characterized by juvenile onset of hyperuricemia, gouty arthritis, and progressive renal failure at an early age. Using a genomewide linkage analysis in three Czech affected families, we have identified, on chromosome 16p11.2, a locus for FJHN and have found evidence for genetic heterogeneity and reduced penetrance of the disease. The maximum two-point LOD score calculated with allowance for heterogeneity (HLOD) was 4.70, obtained at recombination fraction 0, with marker D16S3036; multipoint linkage analysis yielded a maximum HLOD score of 4.76 at the same location. Haplotype analysis defined a 10-cM candidate region between flanking markers D16S501 and D16S3113, exhibiting crossover events with the disease locus. The candidate interval contains several genes expressed in the kidney, two of which-uromodulin and NADP-regulated thyroid-hormone-binding protein-represent promising candidates for further analysis. Familial juvenile hyperuricemic nephropathy (FJHN), or familial juvenile gouty nephropathy (FJGN [MIM 162000]), is an autosomal dominant renal disease characterized by juvenile onset of hyperuricemia, gouty arthritis, and progressive renal failure at an early age. This condition was first noted by Duncan and Dixon (1960). More than 50 kindred originating from various ethnic groups-Whites (for review, see Cameron et al. 1993), Hungarians (Korom et al. 1979), Chinese (Lam and Peh 1995), Japanese (Saeki et al. 1995), and Polynesians (Reiter et al. 1995)-have been described so far. The biochemical hallmarks of the disease are hyperuricemia and reduced fractional excretion of uric acid. Ultrasound imaging studies show decreased kidney size, parenchymal atrophy and abnormal echogenicity in a majority of the patients, and infrequent occurrence of renal cysts
Journal de génétique humaine, 1985
S-100 protein, essentially of astrocytic origin, is present in the amniotic fluid of anencephalic... more S-100 protein, essentially of astrocytic origin, is present in the amniotic fluid of anencephalic fetuses. Its detection reflects tissue necrosis and could be complementary for prenatal diagnosis.
Archives of Disease in Childhood, 2019
ObjectivesTo describe the epidemiology and geographical differences in prevalence of congenital c... more ObjectivesTo describe the epidemiology and geographical differences in prevalence of congenital cerebral anomalies in Europe.Design and settingCongenital cerebral anomalies (International Classification of Diseases, 10th Revision code Q04) recorded in 29 population-based EUROCAT registries conducting surveillance of 1.7 million births per annum (29% of all European births).ParticipantsAll birth outcomes (live births, fetal deaths from 20 weeks gestation and terminations of pregnancy after prenatal diagnosis of a fetal anomaly (TOPFA)) from 2005 to 2014.Main outcome measuresPrevalence, proportion of associated non-cerebral anomalies, prenatal detection rate.Results4927 cases with congenital cerebral anomalies were identified; a prevalence (adjusted for under-reporting) of 9.8 (95% CI: 8.5 to 11.2) per 10 000 births. There was a sixfold difference in prevalence across the registries. Registries with higher proportions of prenatal diagnoses had higher prevalence. Overall, 55% of all ca...
Prenatal Diagnosis, 1984
S-100 protein, which is found essentially in the astrocytes of the nervous system, was assayed in... more S-100 protein, which is found essentially in the astrocytes of the nervous system, was assayed in amniotic fluids by Particle Counting ImmunoAssay. It was present in 19 cases of anencephaly out of 26, in 1 case of open spina bifida out of 5 and in each of the 4 cases of fetal death, whereas it was not detected in the 48 control amniotic fluids collected between the 16th and the 35th week of gestation. Thirty-one amniotic fluids from fetuses with other congenital malformations were devoid of detectable S-100. The presence of S-100 in amniotic fluid of anencephalic fetuses can presumably be considered as a biological sign of necrosis of the exencephalic brain and seems specific to damage of the central nervous system accompanied by neural tube defect.
This report aims at providing healthcare authorities and healthcare professionals with specific r... more This report aims at providing healthcare authorities and healthcare professionals with specific recommendations on the scientific and ethical issues that need to be considered in view of a responsible implementation of preconceptual genetic testing in a reproductive context. The report specifically discusses the framework underpinning the appropriate introduction of such testing and suggests inclusion criteria for diseases that could be targeted by the screening process: (i) severity, (ii) age of onset, (iii) prevalence, (iv) selection of mutations based on clinical significance and (v) treatability.
Journal of Medical Genetics, 1999
Familial adenomatous polyposis (FAP) is characterised by hundreds of colorectal adenomas. Endocri... more Familial adenomatous polyposis (FAP) is characterised by hundreds of colorectal adenomas. Endocrine neoplasms have occasionally been reported, as have gastric polyps, which are usually hamartomatous in the fundus of the stomach and adenomatous in the antrum. A 57 year old man with colorectal, gastric, and periampullary adenomatous polyposis, in association with three bilateral adrenocortical adenomas, is presented. Mutation screening showed a 5960delA germline mutation in the adenomatous polyposis coli (APC) gene predicted to lead to a premature stop codon. This mutation was found in three of the four children of the patient. Western blot analysis of a lymphoblastoid cell line derived from the patient failed to detect any truncated APC polypeptide. This rare 3' mutation is responsible for an unusually complex and late onset phenotype of FAP.
Mutation Research/ …, 1993
Sister-chromatid exchange (SCE) in blood lymphocytes, serum tumors markers, carcinoembryonic anti... more Sister-chromatid exchange (SCE) in blood lymphocytes, serum tumors markers, carcinoembryonic antigen (CEA) and tissue polypeptide antigen (TPA), and urinary excretion of chromium, cobalt and nickel were determined in 26 male workers occupationally exposed to chromium, cobalt and nickel dust and in 25 controls matched for age and smoking habits. The differences in the urinary excretion of metals between exposed persons and controls were statistically significant. An analysis of variance on the SCE rank values revealed that both exposure status (exposed persons vs. controls) and smoking habits (smokers and former smokers vs. never smokers) had a statistically significant effect. For the tumor markers, the analysis of variance did not reveal a statistically significant difference between exposed persons and controls. However, CEA serum levels were significantly correlated not only with smoking habits but also with duration of exposure. As cobalt is only weakly mutagenic, these results suggest that the small amount of absorbed chromium and nickel may have been sufficient to induce SCE. The hypothesis that tumor markers may be increased in groups of subjects exposed to genotoxic substances deserves further study.
Leukemia, 1998
Balanced translocations of 11q23 are associated with specific clinical features and a poor outcom... more Balanced translocations of 11q23 are associated with specific clinical features and a poor outcome, but the relevance of deletions involving 11q23 is not clear. Fifty-seven patients with this deletion were collected by the Workshop, 30 had terminal and 27 had interstitial deletions. Twenty-seven patients had acute lymphoblastic leukemia (ALL), 16 had acute myeloid leukemia (AML), one had acute biphenotypic leukemia, one had acute undifferentiated leukemia and 12 had myelodysplastic syndrome (MDS). ALL patients had a median age of 7 years, median white blood cell count (WBC) of 15 × 10 9 /l, and 10/24 had common ALL. AML patients had a median age of 23 years, a median WBC of 49 × 10 9 /l, and 9/16 had M4 or M5. MDS patients were all adult, median age of 69 years, median WBC of 3 × 10 9 /l, and 7/12 had refractory anemia. The clinical outcome depended on diagnosis: children with ALL had a better prognosis (4/16 relapsed, one died) than AML patients; all adults and children with AML and 5/12 MDS patients died. Fluorescence in situ hybridization (FISH) identified 3 del(11q23) as translocations or insertions. Molecular studies revealed a MLL rearrangement in 8/10 patients. Because the involvement of MLL might be of prognostic relevance, identification of a del(11q23) should be an indication for FISH and molecular studies.
European Journal of Human Genetics, 2013
The intron 22 inversion found in up to 50% of severe hemophilia A patients results from a recombi... more The intron 22 inversion found in up to 50% of severe hemophilia A patients results from a recombination between three intron 22 homologous copies (int22h). This study evaluated the implication of these copies in the formation of extended duplications comprising exons 1-22 of the factor 8 (F8) gene and their association with hemophilia and mental retardation. Two hemophilic patients with moderate and severe phenotypes and a third nonhemophilic patient with developmental delay were studied. All exhibited a duplication of F8 gene exons 1-22 identified by multiplex ligation-dependent probe amplification along with abnormal patterns on Southern blotting and unexpected long-range PCR amplification. Breakpoint analysis using array comparative genomic hybridization was performed to delimit the extent of these rearrangements. These duplications were bounded on one side by the F8 intragenic int22h-1 repeat and on the other side by extragenic int22h-2 or int22h-3 copies. However, the simultaneous identification of a second duplication containing F8 gene exons 2-14 for the moderate patient and the classical intron 22 inversion for the severe patient are considered in this study as the genetic causal defects of hemophilia. This study shows that the well-known int22h copies are involved in extended duplications comprising F8 gene exons 1-22. These specific duplications are probably not responsible for hemophilia and intellectual disability, but should be carefully considered in genetic counseling, while continuing to investigate the causal mutation of hemophilia.
History and Funding Eurocat Northern Netherlands (NNL) started in 1981, and was a member of the E... more History and Funding Eurocat Northern Netherlands (NNL) started in 1981, and was a member of the EUROCAT network since that year. The registry is funded by the Dutch Ministry of Health, Welfare and Sports and is associated with the Department of Genetics of the University Medical Centre of Groningen. Population Coverage The registry is population-based, including babies born to all mothers resident in the registration area. In the beginning, the program covered 7,500 births annually in the province of Groningen and the northern part of the province of Drenthe. From 1989 onwards, coverage was gradually increased to 20,000 births annually in the provinces of Groningen, Friesland and Drenthe. In recent years the number of births in the region decreased to 18.500, approximately 10% of all births in the Netherlands. Home deliveries (25% of births per year) are included and it is estimated that only a few percent of resident mothers would give birth outside the defined registry area.
Bulletin Et Memoires De L Academie Royale De Medecine De Belgique, 2000
Le cancer colorectal est la deuxieme cause de mortalite en Europe occidentale. Notre lecture a po... more Le cancer colorectal est la deuxieme cause de mortalite en Europe occidentale. Notre lecture a pour but de decrire les progres genetiques recents et leur implication dans les mecanismes de la carcinogenese colorectale, ainsi que leurs consequences dans la prise en charge therapeutique et dans les mesures de prevention du cancer colorectal hereditaire non polyposique, ou syndrome HNPCC. L'histoire familiale et les signes cliniques, coliques et extracoliques, qui permettent de suspecter ce syndrome autosomique dominant, sont presentes (criteres d'Amsterdam revus, et ceux de Bethesda). Les six principaux genes MLH1, MSH2, MSH6, PMS2, PMS3 et MSH3, responsables du syndrome HNPCC, sont directement impliques dans le systeme de reparation des mesappariements des bases nucleotidiques, lors de la replication de l'ADN a chaque cycle cellulaire. Un defaut constitutif d'un de ces genes, suivi de la perte de fonction de l'allele homologue, est responsable du phenotype mutateur des tumeurs, qui se manifeste par des variations de taille de sequences repetitives que sont les microsatellites, et par une perte d'expression de proteine specifique au gene implique. Afin de donner une information precise aux cliniciens et aux patients concernes, et en l'absence de criteres absolus de diagnostic du syndrome HNPCC, nous avons developpe, depuis septembre 1998, une strategie de diagnostic genetique du syndrome et de recherche de la mutation responsable pour les deux principaux genes MLH1 et MSH2. Pour les patients, le diagnostic genetique pourrait modifier la prise en charge chirurgicale et le traitement medical, et dans les familles a risque, le diagnostic genetique predictif devrait contribuer tres positivement a la prevention du cancer ».
PloS one, 2018
Surveillance of congenital anomalies is important to identify potential teratogens. This study an... more Surveillance of congenital anomalies is important to identify potential teratogens. This study analysed the prevalence of 61 congenital anomaly subgroups (excluding chromosomal) in 25 population-based EUROCAT registries (1980-2012). Live births, fetal deaths and terminations of pregnancy for fetal anomaly were analysed with multilevel random-effects Poisson regression models. Seventeen anomaly subgroups had statistically significant trends from 2003-2012; 12 increasing and 5 decreasing. The annual increasing prevalence of severe congenital heart defects, single ventricle, atrioventricular septal defects and tetralogy of Fallot of 1.4% (95% CI: 0.7% to 2.0%), 4.6% (1.0% to 8.2%), 3.4% (1.3% to 5.5%) and 4.1% (2.4% to 5.7%) respectively may reflect increases in maternal obesity and diabetes (known risk factors). The increased prevalence of cystic adenomatous malformation of the lung [6.5% (3.5% to 9.4%)] and decreased prevalence of limb reduction defects [-2.8% (-4.2% to -1.5%)] are u...
European Journal of Human Genetics, 2014
Meckel-Gruber Syndrome is a rare autosomal recessive lethal ciliopathy characterized by the triad... more Meckel-Gruber Syndrome is a rare autosomal recessive lethal ciliopathy characterized by the triad of cystic renal dysplasia, occipital encephalocele and postaxial polydactyly. We present the largest population-based epidemiological study to date using data provided by the European Surveillance of Congenital Anomalies (EUROCAT) network. The study population consisted of 191 cases of MKS identified between January 1990 and December 2011 in 34 European registries. The mean prevalence was 2.6 per 100 000 births in a subset of registries with good ascertainment. The prevalence was stable over time, but regional differences were observed. There were 145 (75.9%) terminations of pregnancy after prenatal diagnosis, 13 (6.8%) fetal deaths, 33 (17.3%) live births. In addition to cystic kidneys (97.7%), encephalocele (83.8%) and polydactyly (87.3%), frequent features include other central nervous system anomalies (51.4%), fibrotic/cystic changes of the liver (65.5% of cases with post mortem examination) and orofacial clefts (31.8%). Various other anomalies were present in 64 (37%) patients. As nowadays most patients are detected very early in pregnancy when liver or kidney changes may not yet be developed or may be difficult to assess, none of the anomalies should be considered obligatory for the diagnosis. Most cases (90.2%) are diagnosed prenatally at 14.3 ± 2.6 (range 11-36) gestational weeks and pregnancies are mainly terminated, reducing the number of LB to one-fifth of the total prevalence rate. Early diagnosis is important for timely counseling of affected couples regarding the option of pregnancy termination and prenatal genetic testing in future pregnancies.
The Journal of Rheumatology, 2011
Objective.To compare the distribution of congenital anomalies within the VACTERL association (ver... more Objective.To compare the distribution of congenital anomalies within the VACTERL association (vertebral defects, anal atresia, cardiac, tracheoesophageal, renal, and limb abnormalities) between patients exposed to tumor necrosis factor-α (TNF-α) antagonist and the general population.Methods.Analysis for comparison of proportional differences to a previous publication between anomaly subgroups, according to subgroup definitions of the European Surveillance of Congenital Anomalies (EUROCAT), a population-based database.Results.Most EUROCAT subgroups belonging to the VACTERL association contained only one or 2 records of TNF-α antagonist exposure, so comparison of proportions was imprecise. Only the category “limb abnormalities” showed a significantly higher proportion in the general population.Conclusion.The high number of congenital anomalies belonging to the VACTERL association from a report of pregnancies exposed to TNF-α antagonists could not be confirmed using a population-based ...
BMJ, 2016
ObjeCtives To provide contemporary estimates of the prevalence of microcephaly in Europe, determi... more ObjeCtives To provide contemporary estimates of the prevalence of microcephaly in Europe, determine if the diagnosis of microcephaly is consistent across Europe, and evaluate whether changes in prevalence would be detected using the current European surveillance performed by EUROCAT (the European Surveillance of Congenital Anomalies). Design Questionnaire and population based observational study. setting 24 EUROCAT registries covering 570 000 births annually in 15 countries. PartiCiPants Cases of microcephaly not associated with a genetic condition among live births, fetal deaths from 20 weeks' gestation, and terminations of pregnancy for fetal anomaly at any gestation. Main OutCOMe Measures Prevalence of microcephaly (1 Jan 2003-31 Dec 2012) analysed with random effects Poisson regression models to account for heterogeneity across registries. results 16 registries responded to the questionnaire, of which 44% (7/16) used the EUROCAT definition of microcephaly (a reduction in the size of the brain with a skull circumference more than 3 SD below the mean for sex, age, and ethnic origin), 19% (3/16) used a 2 SD cut off, 31% (5/16) were reliant on the criteria used by individual clinicians, and one changed criteria between 2003 and 2012. Prevalence of microcephaly in Europe was 1.53 (95% confidence interval 1.16 to 1.96) per 10 000 births, with registries varying from 0.4 (0.2 to 0.7) to 4.3 (3.6 to 5.0) per 10 000 (χ 2 =338, df=23, I 2 =93%). Registries with a 3 SD cut off reported a prevalence of 1.74 per 10 000 (0.86 to 2.93) compared with those with the less stringent 2 SD cut off of 1.21 per 10 000 (0.21 to 2.93). The prevalence of microcephaly would need to increase in one year by over 35% in Europe or by over 300% in a single registry to reach statistical significance (P<0.01). COnClusiOns EUROCAT could detect increases in the prevalence of microcephaly from the Zika virus of a similar magnitude to those observed in Brazil. Because of the rarity of microcephaly and discrepant diagnostic criteria, however, the smaller increases expected in Europe would probably not be detected. Clear diagnostic criteria for microcephaly must be adopted across Europe.
Annales de chirurgie de la main et du membre supérieur : organe officiel des sociétés de chirurgie de la main = Annals of hand and upper limb surgery, 1992
The trismus pseudocamptodactyly syndrome also called Hecht syndrome or Dutch-Kentucky syndrome is... more The trismus pseudocamptodactyly syndrome also called Hecht syndrome or Dutch-Kentucky syndrome is characterized by loss of the ability to fully open the mouth (trismus) and a finger contracture with progressive flexion of the fingers upon extension of the wrist (pseudocamptodactyly). Deformities of the foot may be associated e.g. hammer and claw toes, tightening of the muscles of the posterior part of the leg producing an equinovarus foot. The authors presents two affected individuals from one family from which nine members had some involvement. The expression of the syndrome may vary. The pattern of the finger contracture is specific. The inheritance is autosomal dominant.
Cancer Genetics and Cytogenetics, 2001
We report on three cases, two with myelodysplastic syndrome (MDS) and one with acute lymphoblasti... more We report on three cases, two with myelodysplastic syndrome (MDS) and one with acute lymphoblastic leukemia (ALL), displaying trisomy 16 as the sole cytogenetic anomaly. In none of these cases was a concomitant inv(16)(p13q22) detected by fluorescence in situ hybridization (FISH) or reverse transcription polymerase chain reaction (RT-PCR). Summarizing the literature, only six other cases cytogenetically characterized by an isolated trisomy 16 have been reported in hematological malignancies. These patients had either MDS, acute myeloblastic leukemia (AML), myelofibrosis, or ALL. All but one of these cases were aged less than 50.
Cancer Genetics and Cytogenetics, 2007
A retrospective cytogenetic study of acute myeloid leukemias (AML) and myelodysplastic syndromes ... more A retrospective cytogenetic study of acute myeloid leukemias (AML) and myelodysplastic syndromes (MDS) was conducted by the Groupe Francophone de Cytogénétique Hématologique (GFCH) to evaluate the structural abnormalities of chromosome 5 associated with other chromosomal abnormalities, in particular of chromosome 7, in these pathologies. In all, 110 cases of AML/MDS were recruited based on the presence of chromosome 5 abnormalities under conventional cytogenetics and supplemented by a systematic fluorescence in situ hybridization study of chromosomes 5 and 7. The abnormalities of the long arm of chromosome 5 (5q) were deletions of various sizes and sometimes cryptic. The 5q abnormalities were associated with translocations in 54% of cases and were simple deletions in 46%. In 68% of cases, 5q deletions were associated with chromosome 7 abnormalities, and 90% of these presented a complex karyotype. Of the 110 patients, 28 had a hematopoietic disorder secondary to chemotherapy, radiotherapy, or both. Among 82 patients with de novo AML/MDS, 63 were older than 60 years. Chromosomal abnormalities often associated hypodiploidy and chromosome 5 and 7 abnormalities in complex karyotypes, features resembling those of secondary hemopathies. Systematic investigation of the exposure to mutagens and oncogenes is thus essential to specify the factors potentially involved in MDS/AML with 5q abnormalities.
Birth Defects Research Part A: Clinical and Molecular Teratology, 2014
History and Funding Eurocat Northern Netherlands (NNL) started in 1981, and was a member of the E... more History and Funding Eurocat Northern Netherlands (NNL) started in 1981, and was a member of the EUROCAT network since that year. The registry is funded by the Dutch Ministry of Health, Welfare and Sports and is associated with the Department of Genetics of the University Medical Centre of Groningen. Population Coverage The registry is population-based, including babies born to all mothers resident in the registration area. In the beginning, the program covered 7,500 births annually in the province of Groningen and the northern part of the province of Drenthe. From 1989 onwards, coverage was gradually increased to 20,000 births annually in the provinces of Groningen, Friesland and Drenthe. In recent years the number of births in the region decreased to 18.500, approximately 10% of all births in the Netherlands. Home deliveries (25% of births per year) are included and it is estimated that only a few percent of resident mothers would give birth outside the defined registry area.
The American Journal of Human Genetics, 2000
Familial juvenile hyperuricemic nephropathy (FJHN), is an autosomal dominant renal disease charac... more Familial juvenile hyperuricemic nephropathy (FJHN), is an autosomal dominant renal disease characterized by juvenile onset of hyperuricemia, gouty arthritis, and progressive renal failure at an early age. Using a genomewide linkage analysis in three Czech affected families, we have identified, on chromosome 16p11.2, a locus for FJHN and have found evidence for genetic heterogeneity and reduced penetrance of the disease. The maximum two-point LOD score calculated with allowance for heterogeneity (HLOD) was 4.70, obtained at recombination fraction 0, with marker D16S3036; multipoint linkage analysis yielded a maximum HLOD score of 4.76 at the same location. Haplotype analysis defined a 10-cM candidate region between flanking markers D16S501 and D16S3113, exhibiting crossover events with the disease locus. The candidate interval contains several genes expressed in the kidney, two of which-uromodulin and NADP-regulated thyroid-hormone-binding protein-represent promising candidates for further analysis. Familial juvenile hyperuricemic nephropathy (FJHN), or familial juvenile gouty nephropathy (FJGN [MIM 162000]), is an autosomal dominant renal disease characterized by juvenile onset of hyperuricemia, gouty arthritis, and progressive renal failure at an early age. This condition was first noted by Duncan and Dixon (1960). More than 50 kindred originating from various ethnic groups-Whites (for review, see Cameron et al. 1993), Hungarians (Korom et al. 1979), Chinese (Lam and Peh 1995), Japanese (Saeki et al. 1995), and Polynesians (Reiter et al. 1995)-have been described so far. The biochemical hallmarks of the disease are hyperuricemia and reduced fractional excretion of uric acid. Ultrasound imaging studies show decreased kidney size, parenchymal atrophy and abnormal echogenicity in a majority of the patients, and infrequent occurrence of renal cysts
Journal de génétique humaine, 1985
S-100 protein, essentially of astrocytic origin, is present in the amniotic fluid of anencephalic... more S-100 protein, essentially of astrocytic origin, is present in the amniotic fluid of anencephalic fetuses. Its detection reflects tissue necrosis and could be complementary for prenatal diagnosis.
Archives of Disease in Childhood, 2019
ObjectivesTo describe the epidemiology and geographical differences in prevalence of congenital c... more ObjectivesTo describe the epidemiology and geographical differences in prevalence of congenital cerebral anomalies in Europe.Design and settingCongenital cerebral anomalies (International Classification of Diseases, 10th Revision code Q04) recorded in 29 population-based EUROCAT registries conducting surveillance of 1.7 million births per annum (29% of all European births).ParticipantsAll birth outcomes (live births, fetal deaths from 20 weeks gestation and terminations of pregnancy after prenatal diagnosis of a fetal anomaly (TOPFA)) from 2005 to 2014.Main outcome measuresPrevalence, proportion of associated non-cerebral anomalies, prenatal detection rate.Results4927 cases with congenital cerebral anomalies were identified; a prevalence (adjusted for under-reporting) of 9.8 (95% CI: 8.5 to 11.2) per 10 000 births. There was a sixfold difference in prevalence across the registries. Registries with higher proportions of prenatal diagnoses had higher prevalence. Overall, 55% of all ca...
Prenatal Diagnosis, 1984
S-100 protein, which is found essentially in the astrocytes of the nervous system, was assayed in... more S-100 protein, which is found essentially in the astrocytes of the nervous system, was assayed in amniotic fluids by Particle Counting ImmunoAssay. It was present in 19 cases of anencephaly out of 26, in 1 case of open spina bifida out of 5 and in each of the 4 cases of fetal death, whereas it was not detected in the 48 control amniotic fluids collected between the 16th and the 35th week of gestation. Thirty-one amniotic fluids from fetuses with other congenital malformations were devoid of detectable S-100. The presence of S-100 in amniotic fluid of anencephalic fetuses can presumably be considered as a biological sign of necrosis of the exencephalic brain and seems specific to damage of the central nervous system accompanied by neural tube defect.
This report aims at providing healthcare authorities and healthcare professionals with specific r... more This report aims at providing healthcare authorities and healthcare professionals with specific recommendations on the scientific and ethical issues that need to be considered in view of a responsible implementation of preconceptual genetic testing in a reproductive context. The report specifically discusses the framework underpinning the appropriate introduction of such testing and suggests inclusion criteria for diseases that could be targeted by the screening process: (i) severity, (ii) age of onset, (iii) prevalence, (iv) selection of mutations based on clinical significance and (v) treatability.
Journal of Medical Genetics, 1999
Familial adenomatous polyposis (FAP) is characterised by hundreds of colorectal adenomas. Endocri... more Familial adenomatous polyposis (FAP) is characterised by hundreds of colorectal adenomas. Endocrine neoplasms have occasionally been reported, as have gastric polyps, which are usually hamartomatous in the fundus of the stomach and adenomatous in the antrum. A 57 year old man with colorectal, gastric, and periampullary adenomatous polyposis, in association with three bilateral adrenocortical adenomas, is presented. Mutation screening showed a 5960delA germline mutation in the adenomatous polyposis coli (APC) gene predicted to lead to a premature stop codon. This mutation was found in three of the four children of the patient. Western blot analysis of a lymphoblastoid cell line derived from the patient failed to detect any truncated APC polypeptide. This rare 3' mutation is responsible for an unusually complex and late onset phenotype of FAP.
Mutation Research/ …, 1993
Sister-chromatid exchange (SCE) in blood lymphocytes, serum tumors markers, carcinoembryonic anti... more Sister-chromatid exchange (SCE) in blood lymphocytes, serum tumors markers, carcinoembryonic antigen (CEA) and tissue polypeptide antigen (TPA), and urinary excretion of chromium, cobalt and nickel were determined in 26 male workers occupationally exposed to chromium, cobalt and nickel dust and in 25 controls matched for age and smoking habits. The differences in the urinary excretion of metals between exposed persons and controls were statistically significant. An analysis of variance on the SCE rank values revealed that both exposure status (exposed persons vs. controls) and smoking habits (smokers and former smokers vs. never smokers) had a statistically significant effect. For the tumor markers, the analysis of variance did not reveal a statistically significant difference between exposed persons and controls. However, CEA serum levels were significantly correlated not only with smoking habits but also with duration of exposure. As cobalt is only weakly mutagenic, these results suggest that the small amount of absorbed chromium and nickel may have been sufficient to induce SCE. The hypothesis that tumor markers may be increased in groups of subjects exposed to genotoxic substances deserves further study.
Leukemia, 1998
Balanced translocations of 11q23 are associated with specific clinical features and a poor outcom... more Balanced translocations of 11q23 are associated with specific clinical features and a poor outcome, but the relevance of deletions involving 11q23 is not clear. Fifty-seven patients with this deletion were collected by the Workshop, 30 had terminal and 27 had interstitial deletions. Twenty-seven patients had acute lymphoblastic leukemia (ALL), 16 had acute myeloid leukemia (AML), one had acute biphenotypic leukemia, one had acute undifferentiated leukemia and 12 had myelodysplastic syndrome (MDS). ALL patients had a median age of 7 years, median white blood cell count (WBC) of 15 × 10 9 /l, and 10/24 had common ALL. AML patients had a median age of 23 years, a median WBC of 49 × 10 9 /l, and 9/16 had M4 or M5. MDS patients were all adult, median age of 69 years, median WBC of 3 × 10 9 /l, and 7/12 had refractory anemia. The clinical outcome depended on diagnosis: children with ALL had a better prognosis (4/16 relapsed, one died) than AML patients; all adults and children with AML and 5/12 MDS patients died. Fluorescence in situ hybridization (FISH) identified 3 del(11q23) as translocations or insertions. Molecular studies revealed a MLL rearrangement in 8/10 patients. Because the involvement of MLL might be of prognostic relevance, identification of a del(11q23) should be an indication for FISH and molecular studies.
European Journal of Human Genetics, 2013
The intron 22 inversion found in up to 50% of severe hemophilia A patients results from a recombi... more The intron 22 inversion found in up to 50% of severe hemophilia A patients results from a recombination between three intron 22 homologous copies (int22h). This study evaluated the implication of these copies in the formation of extended duplications comprising exons 1-22 of the factor 8 (F8) gene and their association with hemophilia and mental retardation. Two hemophilic patients with moderate and severe phenotypes and a third nonhemophilic patient with developmental delay were studied. All exhibited a duplication of F8 gene exons 1-22 identified by multiplex ligation-dependent probe amplification along with abnormal patterns on Southern blotting and unexpected long-range PCR amplification. Breakpoint analysis using array comparative genomic hybridization was performed to delimit the extent of these rearrangements. These duplications were bounded on one side by the F8 intragenic int22h-1 repeat and on the other side by extragenic int22h-2 or int22h-3 copies. However, the simultaneous identification of a second duplication containing F8 gene exons 2-14 for the moderate patient and the classical intron 22 inversion for the severe patient are considered in this study as the genetic causal defects of hemophilia. This study shows that the well-known int22h copies are involved in extended duplications comprising F8 gene exons 1-22. These specific duplications are probably not responsible for hemophilia and intellectual disability, but should be carefully considered in genetic counseling, while continuing to investigate the causal mutation of hemophilia.
History and Funding Eurocat Northern Netherlands (NNL) started in 1981, and was a member of the E... more History and Funding Eurocat Northern Netherlands (NNL) started in 1981, and was a member of the EUROCAT network since that year. The registry is funded by the Dutch Ministry of Health, Welfare and Sports and is associated with the Department of Genetics of the University Medical Centre of Groningen. Population Coverage The registry is population-based, including babies born to all mothers resident in the registration area. In the beginning, the program covered 7,500 births annually in the province of Groningen and the northern part of the province of Drenthe. From 1989 onwards, coverage was gradually increased to 20,000 births annually in the provinces of Groningen, Friesland and Drenthe. In recent years the number of births in the region decreased to 18.500, approximately 10% of all births in the Netherlands. Home deliveries (25% of births per year) are included and it is estimated that only a few percent of resident mothers would give birth outside the defined registry area.