Alvaro Mesoraca - Academia.edu (original) (raw)

Papers by Alvaro Mesoraca

Research paper thumbnail of De novo 3q13.13q21.2 interstitial deletion and paternal 12p13.3 microdeletion in a fetus with dysplasia of the corpus callosum and ventriculomegaly: A case report

Experimental and Therapeutic Medicine

Chromosome 3q syndrome is a well-known genetic condition caused by interstitial deletion in the l... more Chromosome 3q syndrome is a well-known genetic condition caused by interstitial deletion in the long arm of chromosome 3. The phenotype of this syndrome is variable and the great variability in the extent of these deletions leads to a wide spectrum of clinical manifestations. Terminal 12p deletion represents one of the rarest subtelomeric imbalances; patients with distal monosomy 12p present different phenotypes ranging from muscular hypotonia to autism spectrum disorders. The present study reported a prenatal diagnosis of a male fetus presenting ultrasound evidence of corpus callosum dysplasia and ventriculomegaly showing a 3q13q21.2 deletion and a 12p13.33 microdeletion paternally inherited. Among several features previously attributed to the terminal deletion of 3q, corpus callosum dysplasia and ventriculomegaly have rarely been reported together. As the 12p13.33 microdeletion in the father was associated only with muscular hypotonia and joint laxity, the involvement of terminal 12p deletions in the clinical features of the fetus was not possible to verify during the prenatal period. The present case report may provide a reference for prenatal diagnosis and genetic counseling in patients who present 3q13q21.2 deletions and 12p13.33 microdeletion.

Research paper thumbnail of Letter to the Editor: The Clinical Features of SARS-CoV-2 Infection Are Becoming Milder with Limited Symptomatic Effects

Research paper thumbnail of Retrospective study evaluating the performance of a first-trimester combined screening for trisomy 21 in an Italian unselected population

Journal of prenatal medicine

to assess the performance of a combined first-trimester screening for trisomy 21 in an unselected... more to assess the performance of a combined first-trimester screening for trisomy 21 in an unselected Italian population referred to a specialized private center for prenatal medicine. a retrospective validation of first-trimester screening algorithms [risk calculation based on maternal age and nuchal translucency (NT) alone, maternal age and serum parameters (free β-hCG and PAPP-A) alone and a combination of both] for fetal aneuploidies evaluated in an unselected Italian population at Artemisia Fetal-Maternal Medical Centre in Rome. All measurements were performed between 11(+0) and 13(+6) weeks of gestation, between April 2007 and December 2008. of 3,610 single fetuses included in the study, we had a complete follow-up on 2,984. Fourteen of 17 cases of trisomy 21 were detected when a cut-off of 1:300 was applied [detection rate (DR) 82.4%, 95% confidence interval (CI) 64.2-100; false-positive rate (FPR) 4.7%, 95% CI 3.9-5.4; false-negative rate (FNR) 17.6%, 95% CI 0-35.8%]. in our stu...

Research paper thumbnail of Retrospective study evaluating the performance of a first-trimester combined screening for trisomy 21 in an Italian unselected population

Journal of prenatal medicine

to assess the performance of a combined first-trimester screening for trisomy 21 in an unselected... more to assess the performance of a combined first-trimester screening for trisomy 21 in an unselected Italian population referred to a specialized private center for prenatal medicine. a retrospective validation of first-trimester screening algorithms [risk calculation based on maternal age and nuchal translucency (NT) alone, maternal age and serum parameters (free β-hCG and PAPP-A) alone and a combination of both] for fetal aneuploidies evaluated in an unselected Italian population at Artemisia Fetal-Maternal Medical Centre in Rome. All measurements were performed between 11(+0) and 13(+6) weeks of gestation, between April 2007 and December 2008. of 3,610 single fetuses included in the study, we had a complete follow-up on 2,984. Fourteen of 17 cases of trisomy 21 were detected when a cut-off of 1:300 was applied [detection rate (DR) 82.4%, 95% confidence interval (CI) 64.2-100; false-positive rate (FPR) 4.7%, 95% CI 3.9-5.4; false-negative rate (FNR) 17.6%, 95% CI 0-35.8%]. in our stu...

Research paper thumbnail of Comparative study of aCGH and Next Generation Sequencing (NGS) for chromosomal microdeletion and microduplication screening

Journal of prenatal medicine

prenatal genetic diagnosis of rare disorders is undergoing in recent years a significant enhancem... more prenatal genetic diagnosis of rare disorders is undergoing in recent years a significant enhancement through the application of methods of massive parallel sequencing. Despite the quantity and quality of the data produced, just few analytical tools and software have been developed in order to identify structural and numerical chromosomal anomalies through NGS, mostly not compatible with benchtop NGS platform and routine clinical diagnosis. we developed technical, bioinformatic, interpretive and validation pipelines for Next Generation Sequencing to identify SNPs, indels, aneuploidies, and CNVs (Copy Number Variations). we show a new targeted resequencing approach applied to prenatal diagnosis. For sample processing we used an enrichment method for 4,813 genes library preparation; after sequencing our bioinformatic pipelines allowed both SNPs analysis for approximately thirty diseases or diseases family involved in fetus development and numerical chromosomal anomalies screening. resu...

Research paper thumbnail of A new approach for Next Generation Sequencing in prenatal diagnosis applied to a case of Charcot-Marie-Tooth syndrome

Prenatal Diagnosis, 2015

ABSTRACT

Research paper thumbnail of Introducing the next generation sequencing in genomic amnio and villuos sampling. The so called "Next Generation Prenatal Diagnosis" (NGPD)

Journal of prenatal medicine, 2014

Research paper thumbnail of Significance of heterozygosis M34T mutation of GJB2 gene in non-syndromic congenital deafness. Retrospective analysis of 12,472 samples of amniotic fluid

Journal of prenatal medicine, 2013

to determinate the role of heterozygosis of M34T mutation of GJB2 gene in non syndromic congenita... more to determinate the role of heterozygosis of M34T mutation of GJB2 gene in non syndromic congenital deafness. retrospective study between March 2010 and June 2013. Molecular screening for 35delG and M34T mutations of the GJB2 gene was offered to all women undergoing to second trimester genetic amniocentesis. Patients were excluded from the study group if one of the following conditions were present: infections, fetal abnormalities, family history for congenital deafness, diagnosis of chromosomal abnormalities, and consanguinity between parents. a total of 12.472 Caucasian women gave informed consent for this test. Seventy-seven cases were excluded. From the 12.395 amniotic fluid analysis remained, the following was found: 2 cases of 35delG homozygosis and 352 cases of heterozygous carriers (42 M34T mutation, 298 35delG mutation, 12 double heterozygosis M34T/35delG). The follow up in first year of life in the 42 newborns with heterozygosis for M34T mutation showed a mild deafness in 2...

Research paper thumbnail of Sudden intrauterine unexplained death: time for change

Journal of prenatal medicine, 2012

Research paper thumbnail of Discordance between karyotype from amniotic fluid and postnatal lymphocyte cultures

Journal of prenatal medicine, 2012

Discordance between karyotype seen from amniocentesis and from neonatal blood is a very unusual c... more Discordance between karyotype seen from amniocentesis and from neonatal blood is a very unusual condition with different possible causes.We present a case of discordance between prenatal cytogenetic diagnosis from amniotic fluid and post-natal cytogenetic diagnosis from lymphocyte cultures.

Research paper thumbnail of A case report of a meiotic segregation study on a small supernumerary marker chromosome

Journal of prenatal medicine, 2007

Small supernumerary marker chromosomes (sSMCs) have been described from all human chromosomes wit... more Small supernumerary marker chromosomes (sSMCs) have been described from all human chromosomes with different sizes and shapes. However, it is difficult to know the clinical manifestations associated with them, because such knowledge depends on the size, presence of euchromatic material, degree of mosaicism and/or uniparental disomy (UPD).A case report of a familial small supernumerary marker chromosome (sSMC) through a structural and a segregation study is reported.

Research paper thumbnail of Isolation of amniotic fluid-derived mesenchymal stem cells

Journal of prenatal medicine, 2007

Research paper thumbnail of The use of DHPLC (Denaturing High Performance Liquid Chromatography) in II level screening of the CFTR gene in Prenatal Diagnosis

Journal of prenatal medicine, 2010

The aim of the study is to evaluate the role of Denaturing High Performance Liquid Chromatography... more The aim of the study is to evaluate the role of Denaturing High Performance Liquid Chromatography (DHPLC) in the second level screening of the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene. A 9-month prospective study, between June 2008 and March 2009 at Artemisia Fetal Medical Centre, included 3829 samples of amniotic fluid collected from women undergoing mid-trimester amniocentesis.The genetic diagnosis of CF was based on research of the main mutations of the CFTR gene on fetal DNA extracted from the amniocytes, (first level screening) using different commercial diagnostic systems. A second level screening using DHPLC, on the amniotic fluid and on a blood sample from the couple, was offered in case of fetuses heterozygous at first level screening. Of 3829 fetuses, 134 were found to be positive, 129 heterozygous and 5 affected. Of the 129 couples, following appropriate genetic counselling, 53 requested a second level screening. Through the use of DHPLC, 44 couples...

Research paper thumbnail of Now you can! Reality & Future Applications of array CGH in prenatal diagnosis

Journal of prenatal medicine, 2009

Research paper thumbnail of Prenatal screening of Cystic Fibrosis: a single centre experience

Journal of prenatal medicine, 2008

The gene responsible for the pathogenesis of cystic fibrosis has been known for over 15 years and... more The gene responsible for the pathogenesis of cystic fibrosis has been known for over 15 years and represent the most common autosomal recessive disease in the european population. We aimed to investigate the incidence of this condition during fetal life. In the past 10 years we examined in our centre 25393 fetuses of women underwent to amniocentesis. We carried out the examination of the most frequent mutations which enable, according to the literature data, the identification of almost 80% of the affected alleles. We identified 922 heterozygous and 9 homozygous for the mutation. The frequency of heterozygousin the examined sample was 1/27,5 while that of the affected was 1/2821. We encourage new thoughts regarding the diagnostic validity of the most frequent panel of mutations among the italian population in order to exclude never encountered mutations and the insertion of other more significant mutations.

Research paper thumbnail of Six consecutive false positive cases from cell-free fetal DNA testing in a single referring centre

Journal of Prenatal Medicine, 2014

recent studies have proposed the introduction of cell-free fetal DNA testing (NIPT-Non Invasive P... more recent studies have proposed the introduction of cell-free fetal DNA testing (NIPT-Non Invasive Prenatal Testing) in routine clinical practice emphasizing its high sensibility and specificity. In any case, false positive and false negative findings may result from placental mosaicism, because cell-free fetal DNA originates mainly from placenta. WE REPORT SIX CASES OF WOMEN WHO UNDERWENT CHORIONIC VILLUS SAMPLING (CVS) OR AMNIOCENTESIS TO CONFIRM THE RESULTS FROM NIPT: two Turner syndromes, two Triple X, one Patau syndrome, one Edward syndrome. using classic cytogenetic analysis and, also, Array - Comparative Genomic Hybridization (Array CGH) the karyotype of all 5 fetuses was found to be normal. results from NIPT must always be confirmed by invasive prenatal diagnosis. It is mandatory to inform the patient that the CVS and amniocentesis still represent the only form of prenatal diagnostic test available.

Research paper thumbnail of Mutation analysis of the CLCN1 gene in ITALIAN patients affected by thomsen myotonia congenita and generalized becker myotonia

Neuromuscular Disorders, 1996

Research paper thumbnail of Next generation sequencing in the identification of a rare genetic disease from preconceptional couple screening to preimplantation genetic diagnosis

Journal of Prenatal Medicine, 2014

the use of Next Generation Sequencing (NGS) in the diagnosis of rare genetic pathologies is becom... more the use of Next Generation Sequencing (NGS) in the diagnosis of rare genetic pathologies is becoming ever more widespread in clinical practice. The following study reports the first case of preimplantation diagnosis through NGS of a form of LAMA2-related muscular dystrophy. a couple came to our Reproductive Medicine Centre for a preconceptional genetic consultation and for advice regarding secondary infertility. The couple already had a 3-year-old child who was suffering from a form of muscular dystrophy that has yet to be genetically defined. The disease had been diagnosed at the age of 6 months. A blood sample was taken from both parents and the child in order to analyze the DNA through the Illumina NextSeq 500 platform and an enrichment protocol, Trusight One Sequencing Panel, created by Illumina for the simultaneous sequencing of the exon regions of 4,813 clinically relevant genes. This led to the identification of 2 point mutations in the LAMA2 gene, each inherited by a parent. The couple then underwent a cycle of IVF (in vitro fertilization). A preimplantation genetic diagnosis was carried out on the embryos obtained after setting up a protocol for the analysis of a point mutation in the LAMA2 gene, (this mutation has yet to be described in literature) and the normal embryos together with the recessive LAMA2-related muscular dystrophy related carriers were transferred. There were no complications during pregnancy, which terminated with a cesarean section at 39 weeks and the birth of healthy 3430-gram baby. given its robustness, reliability and reproducibility, NGS could also be useful in prenatal diagnosis. This technique could guarantee an ample and quick analysis of the genes involved in development, making it possible to organize medical interventions during pregnancy and after birth.

Research paper thumbnail of OP21.12: Comparasion of quantitative fluorescent PCR and cytogenetic analysis for common autosomal aneuploidies and gonosomal chromosomal disorders in 18 030 amniotic fluids of unselected fetuses

Ultrasound in Obstetrics and Gynecology, 2007

Methods: A prospective cohort study was designed. Twodimensional ultrasound (2D) (193 women) and ... more Methods: A prospective cohort study was designed. Twodimensional ultrasound (2D) (193 women) and three-dimensional ultrasound (3D) were performed (100 pregnant patients). Excluded were those with multiple pregnancies, congenital anomalies, abnormal karyotype and poly or oligohydramnios. For the 2D ultrasound we used the parasagittal plane in order to view and measure the soleus muscle. Measurements were carried out between the tibia and outer border of the skin, at the point of the upper third of the tibia. For the 3D ultrasound multiplanar images were used to measure the popliteus and the gastrocnemius. Results: The soleus muscle width increases with increasing gestational age (r 2 = 0.9403; P = 0.0001). Also, the muscle and bone ratio decreases statistically significantly throughout pregnancy, but the slope is insignificant (r 2 = 0.2198; P = 0.001). The popliteus and the gastrocnemius muscles' width also increase with increasing gestational age (r 2 = 0.857, P < 0.0001), as does the ratio between soleus and the gastrocnemius muscles and the tibia (r 2 = 0.158, P = 0.001). Conclusions: The present data provide a nomogram of the calf's depth with a direct correlation between muscle growth and gestational age. Measurements of calf growth performed by a combination of 2D and 3D ultrasound are highly reproducible with relative ease, between 15 and 42 weeks' gestation. This nomogram can offer a basis for normal calf development and may assist in distinguishing between different etiologies leading to club foot and other joint contractures.

Research paper thumbnail of ULTRASOUND AND MOLECULAR MID–TRIMESTER PRENATAL DIAGNOSIS OFDE NOVO ACHONDROPLASIA

Prenatal Diagnosis, 1996

In a low-risk pregnant patient at 21 weeks&#39; gestation, ultrasound revealed shortening of ... more In a low-risk pregnant patient at 21 weeks&#39; gestation, ultrasound revealed shortening of fetal long bones compatible with achondroplasia. Funipuncture was performed and DNA analysis of fetal blood demonstrated the presence of the GR380R fibroblast growth factor receptor 3 (FGFR3), which is specifically associated with achondroplasia. After termination of the pregnancy, necropsy confirmed the prenatal diagnosis. A certain sonographic diagnosis of fetal de novo achondroplasia is rarely possible prior to viability. The specificity of the FGFR3 causative mutation has added a new diagnostic option which can be applied prenatally for diagnostic validation.

Research paper thumbnail of De novo 3q13.13q21.2 interstitial deletion and paternal 12p13.3 microdeletion in a fetus with dysplasia of the corpus callosum and ventriculomegaly: A case report

Experimental and Therapeutic Medicine

Chromosome 3q syndrome is a well-known genetic condition caused by interstitial deletion in the l... more Chromosome 3q syndrome is a well-known genetic condition caused by interstitial deletion in the long arm of chromosome 3. The phenotype of this syndrome is variable and the great variability in the extent of these deletions leads to a wide spectrum of clinical manifestations. Terminal 12p deletion represents one of the rarest subtelomeric imbalances; patients with distal monosomy 12p present different phenotypes ranging from muscular hypotonia to autism spectrum disorders. The present study reported a prenatal diagnosis of a male fetus presenting ultrasound evidence of corpus callosum dysplasia and ventriculomegaly showing a 3q13q21.2 deletion and a 12p13.33 microdeletion paternally inherited. Among several features previously attributed to the terminal deletion of 3q, corpus callosum dysplasia and ventriculomegaly have rarely been reported together. As the 12p13.33 microdeletion in the father was associated only with muscular hypotonia and joint laxity, the involvement of terminal 12p deletions in the clinical features of the fetus was not possible to verify during the prenatal period. The present case report may provide a reference for prenatal diagnosis and genetic counseling in patients who present 3q13q21.2 deletions and 12p13.33 microdeletion.

Research paper thumbnail of Letter to the Editor: The Clinical Features of SARS-CoV-2 Infection Are Becoming Milder with Limited Symptomatic Effects

Research paper thumbnail of Retrospective study evaluating the performance of a first-trimester combined screening for trisomy 21 in an Italian unselected population

Journal of prenatal medicine

to assess the performance of a combined first-trimester screening for trisomy 21 in an unselected... more to assess the performance of a combined first-trimester screening for trisomy 21 in an unselected Italian population referred to a specialized private center for prenatal medicine. a retrospective validation of first-trimester screening algorithms [risk calculation based on maternal age and nuchal translucency (NT) alone, maternal age and serum parameters (free β-hCG and PAPP-A) alone and a combination of both] for fetal aneuploidies evaluated in an unselected Italian population at Artemisia Fetal-Maternal Medical Centre in Rome. All measurements were performed between 11(+0) and 13(+6) weeks of gestation, between April 2007 and December 2008. of 3,610 single fetuses included in the study, we had a complete follow-up on 2,984. Fourteen of 17 cases of trisomy 21 were detected when a cut-off of 1:300 was applied [detection rate (DR) 82.4%, 95% confidence interval (CI) 64.2-100; false-positive rate (FPR) 4.7%, 95% CI 3.9-5.4; false-negative rate (FNR) 17.6%, 95% CI 0-35.8%]. in our stu...

Research paper thumbnail of Retrospective study evaluating the performance of a first-trimester combined screening for trisomy 21 in an Italian unselected population

Journal of prenatal medicine

to assess the performance of a combined first-trimester screening for trisomy 21 in an unselected... more to assess the performance of a combined first-trimester screening for trisomy 21 in an unselected Italian population referred to a specialized private center for prenatal medicine. a retrospective validation of first-trimester screening algorithms [risk calculation based on maternal age and nuchal translucency (NT) alone, maternal age and serum parameters (free β-hCG and PAPP-A) alone and a combination of both] for fetal aneuploidies evaluated in an unselected Italian population at Artemisia Fetal-Maternal Medical Centre in Rome. All measurements were performed between 11(+0) and 13(+6) weeks of gestation, between April 2007 and December 2008. of 3,610 single fetuses included in the study, we had a complete follow-up on 2,984. Fourteen of 17 cases of trisomy 21 were detected when a cut-off of 1:300 was applied [detection rate (DR) 82.4%, 95% confidence interval (CI) 64.2-100; false-positive rate (FPR) 4.7%, 95% CI 3.9-5.4; false-negative rate (FNR) 17.6%, 95% CI 0-35.8%]. in our stu...

Research paper thumbnail of Comparative study of aCGH and Next Generation Sequencing (NGS) for chromosomal microdeletion and microduplication screening

Journal of prenatal medicine

prenatal genetic diagnosis of rare disorders is undergoing in recent years a significant enhancem... more prenatal genetic diagnosis of rare disorders is undergoing in recent years a significant enhancement through the application of methods of massive parallel sequencing. Despite the quantity and quality of the data produced, just few analytical tools and software have been developed in order to identify structural and numerical chromosomal anomalies through NGS, mostly not compatible with benchtop NGS platform and routine clinical diagnosis. we developed technical, bioinformatic, interpretive and validation pipelines for Next Generation Sequencing to identify SNPs, indels, aneuploidies, and CNVs (Copy Number Variations). we show a new targeted resequencing approach applied to prenatal diagnosis. For sample processing we used an enrichment method for 4,813 genes library preparation; after sequencing our bioinformatic pipelines allowed both SNPs analysis for approximately thirty diseases or diseases family involved in fetus development and numerical chromosomal anomalies screening. resu...

Research paper thumbnail of A new approach for Next Generation Sequencing in prenatal diagnosis applied to a case of Charcot-Marie-Tooth syndrome

Prenatal Diagnosis, 2015

ABSTRACT

Research paper thumbnail of Introducing the next generation sequencing in genomic amnio and villuos sampling. The so called "Next Generation Prenatal Diagnosis" (NGPD)

Journal of prenatal medicine, 2014

Research paper thumbnail of Significance of heterozygosis M34T mutation of GJB2 gene in non-syndromic congenital deafness. Retrospective analysis of 12,472 samples of amniotic fluid

Journal of prenatal medicine, 2013

to determinate the role of heterozygosis of M34T mutation of GJB2 gene in non syndromic congenita... more to determinate the role of heterozygosis of M34T mutation of GJB2 gene in non syndromic congenital deafness. retrospective study between March 2010 and June 2013. Molecular screening for 35delG and M34T mutations of the GJB2 gene was offered to all women undergoing to second trimester genetic amniocentesis. Patients were excluded from the study group if one of the following conditions were present: infections, fetal abnormalities, family history for congenital deafness, diagnosis of chromosomal abnormalities, and consanguinity between parents. a total of 12.472 Caucasian women gave informed consent for this test. Seventy-seven cases were excluded. From the 12.395 amniotic fluid analysis remained, the following was found: 2 cases of 35delG homozygosis and 352 cases of heterozygous carriers (42 M34T mutation, 298 35delG mutation, 12 double heterozygosis M34T/35delG). The follow up in first year of life in the 42 newborns with heterozygosis for M34T mutation showed a mild deafness in 2...

Research paper thumbnail of Sudden intrauterine unexplained death: time for change

Journal of prenatal medicine, 2012

Research paper thumbnail of Discordance between karyotype from amniotic fluid and postnatal lymphocyte cultures

Journal of prenatal medicine, 2012

Discordance between karyotype seen from amniocentesis and from neonatal blood is a very unusual c... more Discordance between karyotype seen from amniocentesis and from neonatal blood is a very unusual condition with different possible causes.We present a case of discordance between prenatal cytogenetic diagnosis from amniotic fluid and post-natal cytogenetic diagnosis from lymphocyte cultures.

Research paper thumbnail of A case report of a meiotic segregation study on a small supernumerary marker chromosome

Journal of prenatal medicine, 2007

Small supernumerary marker chromosomes (sSMCs) have been described from all human chromosomes wit... more Small supernumerary marker chromosomes (sSMCs) have been described from all human chromosomes with different sizes and shapes. However, it is difficult to know the clinical manifestations associated with them, because such knowledge depends on the size, presence of euchromatic material, degree of mosaicism and/or uniparental disomy (UPD).A case report of a familial small supernumerary marker chromosome (sSMC) through a structural and a segregation study is reported.

Research paper thumbnail of Isolation of amniotic fluid-derived mesenchymal stem cells

Journal of prenatal medicine, 2007

Research paper thumbnail of The use of DHPLC (Denaturing High Performance Liquid Chromatography) in II level screening of the CFTR gene in Prenatal Diagnosis

Journal of prenatal medicine, 2010

The aim of the study is to evaluate the role of Denaturing High Performance Liquid Chromatography... more The aim of the study is to evaluate the role of Denaturing High Performance Liquid Chromatography (DHPLC) in the second level screening of the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene. A 9-month prospective study, between June 2008 and March 2009 at Artemisia Fetal Medical Centre, included 3829 samples of amniotic fluid collected from women undergoing mid-trimester amniocentesis.The genetic diagnosis of CF was based on research of the main mutations of the CFTR gene on fetal DNA extracted from the amniocytes, (first level screening) using different commercial diagnostic systems. A second level screening using DHPLC, on the amniotic fluid and on a blood sample from the couple, was offered in case of fetuses heterozygous at first level screening. Of 3829 fetuses, 134 were found to be positive, 129 heterozygous and 5 affected. Of the 129 couples, following appropriate genetic counselling, 53 requested a second level screening. Through the use of DHPLC, 44 couples...

Research paper thumbnail of Now you can! Reality & Future Applications of array CGH in prenatal diagnosis

Journal of prenatal medicine, 2009

Research paper thumbnail of Prenatal screening of Cystic Fibrosis: a single centre experience

Journal of prenatal medicine, 2008

The gene responsible for the pathogenesis of cystic fibrosis has been known for over 15 years and... more The gene responsible for the pathogenesis of cystic fibrosis has been known for over 15 years and represent the most common autosomal recessive disease in the european population. We aimed to investigate the incidence of this condition during fetal life. In the past 10 years we examined in our centre 25393 fetuses of women underwent to amniocentesis. We carried out the examination of the most frequent mutations which enable, according to the literature data, the identification of almost 80% of the affected alleles. We identified 922 heterozygous and 9 homozygous for the mutation. The frequency of heterozygousin the examined sample was 1/27,5 while that of the affected was 1/2821. We encourage new thoughts regarding the diagnostic validity of the most frequent panel of mutations among the italian population in order to exclude never encountered mutations and the insertion of other more significant mutations.

Research paper thumbnail of Six consecutive false positive cases from cell-free fetal DNA testing in a single referring centre

Journal of Prenatal Medicine, 2014

recent studies have proposed the introduction of cell-free fetal DNA testing (NIPT-Non Invasive P... more recent studies have proposed the introduction of cell-free fetal DNA testing (NIPT-Non Invasive Prenatal Testing) in routine clinical practice emphasizing its high sensibility and specificity. In any case, false positive and false negative findings may result from placental mosaicism, because cell-free fetal DNA originates mainly from placenta. WE REPORT SIX CASES OF WOMEN WHO UNDERWENT CHORIONIC VILLUS SAMPLING (CVS) OR AMNIOCENTESIS TO CONFIRM THE RESULTS FROM NIPT: two Turner syndromes, two Triple X, one Patau syndrome, one Edward syndrome. using classic cytogenetic analysis and, also, Array - Comparative Genomic Hybridization (Array CGH) the karyotype of all 5 fetuses was found to be normal. results from NIPT must always be confirmed by invasive prenatal diagnosis. It is mandatory to inform the patient that the CVS and amniocentesis still represent the only form of prenatal diagnostic test available.

Research paper thumbnail of Mutation analysis of the CLCN1 gene in ITALIAN patients affected by thomsen myotonia congenita and generalized becker myotonia

Neuromuscular Disorders, 1996

Research paper thumbnail of Next generation sequencing in the identification of a rare genetic disease from preconceptional couple screening to preimplantation genetic diagnosis

Journal of Prenatal Medicine, 2014

the use of Next Generation Sequencing (NGS) in the diagnosis of rare genetic pathologies is becom... more the use of Next Generation Sequencing (NGS) in the diagnosis of rare genetic pathologies is becoming ever more widespread in clinical practice. The following study reports the first case of preimplantation diagnosis through NGS of a form of LAMA2-related muscular dystrophy. a couple came to our Reproductive Medicine Centre for a preconceptional genetic consultation and for advice regarding secondary infertility. The couple already had a 3-year-old child who was suffering from a form of muscular dystrophy that has yet to be genetically defined. The disease had been diagnosed at the age of 6 months. A blood sample was taken from both parents and the child in order to analyze the DNA through the Illumina NextSeq 500 platform and an enrichment protocol, Trusight One Sequencing Panel, created by Illumina for the simultaneous sequencing of the exon regions of 4,813 clinically relevant genes. This led to the identification of 2 point mutations in the LAMA2 gene, each inherited by a parent. The couple then underwent a cycle of IVF (in vitro fertilization). A preimplantation genetic diagnosis was carried out on the embryos obtained after setting up a protocol for the analysis of a point mutation in the LAMA2 gene, (this mutation has yet to be described in literature) and the normal embryos together with the recessive LAMA2-related muscular dystrophy related carriers were transferred. There were no complications during pregnancy, which terminated with a cesarean section at 39 weeks and the birth of healthy 3430-gram baby. given its robustness, reliability and reproducibility, NGS could also be useful in prenatal diagnosis. This technique could guarantee an ample and quick analysis of the genes involved in development, making it possible to organize medical interventions during pregnancy and after birth.

Research paper thumbnail of OP21.12: Comparasion of quantitative fluorescent PCR and cytogenetic analysis for common autosomal aneuploidies and gonosomal chromosomal disorders in 18 030 amniotic fluids of unselected fetuses

Ultrasound in Obstetrics and Gynecology, 2007

Methods: A prospective cohort study was designed. Twodimensional ultrasound (2D) (193 women) and ... more Methods: A prospective cohort study was designed. Twodimensional ultrasound (2D) (193 women) and three-dimensional ultrasound (3D) were performed (100 pregnant patients). Excluded were those with multiple pregnancies, congenital anomalies, abnormal karyotype and poly or oligohydramnios. For the 2D ultrasound we used the parasagittal plane in order to view and measure the soleus muscle. Measurements were carried out between the tibia and outer border of the skin, at the point of the upper third of the tibia. For the 3D ultrasound multiplanar images were used to measure the popliteus and the gastrocnemius. Results: The soleus muscle width increases with increasing gestational age (r 2 = 0.9403; P = 0.0001). Also, the muscle and bone ratio decreases statistically significantly throughout pregnancy, but the slope is insignificant (r 2 = 0.2198; P = 0.001). The popliteus and the gastrocnemius muscles' width also increase with increasing gestational age (r 2 = 0.857, P < 0.0001), as does the ratio between soleus and the gastrocnemius muscles and the tibia (r 2 = 0.158, P = 0.001). Conclusions: The present data provide a nomogram of the calf's depth with a direct correlation between muscle growth and gestational age. Measurements of calf growth performed by a combination of 2D and 3D ultrasound are highly reproducible with relative ease, between 15 and 42 weeks' gestation. This nomogram can offer a basis for normal calf development and may assist in distinguishing between different etiologies leading to club foot and other joint contractures.

Research paper thumbnail of ULTRASOUND AND MOLECULAR MID–TRIMESTER PRENATAL DIAGNOSIS OFDE NOVO ACHONDROPLASIA

Prenatal Diagnosis, 1996

In a low-risk pregnant patient at 21 weeks&#39; gestation, ultrasound revealed shortening of ... more In a low-risk pregnant patient at 21 weeks&#39; gestation, ultrasound revealed shortening of fetal long bones compatible with achondroplasia. Funipuncture was performed and DNA analysis of fetal blood demonstrated the presence of the GR380R fibroblast growth factor receptor 3 (FGFR3), which is specifically associated with achondroplasia. After termination of the pregnancy, necropsy confirmed the prenatal diagnosis. A certain sonographic diagnosis of fetal de novo achondroplasia is rarely possible prior to viability. The specificity of the FGFR3 causative mutation has added a new diagnostic option which can be applied prenatally for diagnostic validation.