Domenici Kulikowski - Academia.edu (original) (raw)

Papers by Domenici Kulikowski

Research paper thumbnail of Genetic analysis of products of conception. Should we abandon classic karyotyping methodology?

Einstein (São Paulo)

Comparar os resultados obtidos pela metodologia clássica e molecular na análise de produtos de co... more Comparar os resultados obtidos pela metodologia clássica e molecular na análise de produtos de concepção, além das vantagens e desvantagens de cada método. Métodos: Análise retrospectiva não randomizada dos resultados obtidos a partir de amostras de produto de concepção submetidas à avaliação genética, de 2012 a 2017. As análises foram realizadas por citogenética clássica e/ou análise cromossômica de microarray ou arrays. Resultados: Quarenta amostras foram analisadas por citogenética, das quais 10% não apresentaram crescimento celular, 50% apresentaram resultados normais, e 40% apresentaram anormalidades. Dos 41 casos encaminhados para análise por array, não foi possível obter resultados em 7,3%, 39,5% eram normais, e 60,5% apresentavam alterações. Não houve diferença estatística entre os resultados (p=0,89). A maioria dos resultados anormais foi observada até a nona semana de gestação. Uma perda fetal mais tardia foi observada na 28ª semana de gestação, com cariótipo 46,XX,del(15) (q26.2-qter). Os números observados corroboraram a literatura mundial. Conclusão: As técnicas de citogenética clássica e análise por array mostraram resultados comparáveis no tipo de alteração observada. O array é preferível à cultura de células em abortos tardios, enquanto a citogenética é mais capaz de mostrar poliploidias. Ambos têm as mesmas taxas de falha de crescimento quando o tecido do produto de concepção não é coletado adequadamente.

Research paper thumbnail of Fetal gastroschisis: Maternal and fetal methylation profile

Prenatal Diagnosis, 2021

The purpose of this study was to describe the genomic deoxyribonucleic acid (DNA) methylation pro... more The purpose of this study was to describe the genomic deoxyribonucleic acid (DNA) methylation profile in fetuses with gastroschisis, determine whether the profile was inherited, and investigate any possible correlations with maternal risk factors.

Research paper thumbnail of CLINICAL REPORT A Rare Case of Trisomy 15pter-q21.2 Due to a De Novo

be associated with an abnormal phenotype, depending on the presence of euchromatin, on their chro... more be associated with an abnormal phenotype, depending on the presence of euchromatin, on their chromosomal origin and whether they are inherited. Over 80 % of sSMCs are derived from acrocentric chromosomes and half of them include the short arm of chromosome 15. Generally, they appear as bisatellited isodicentric marker chromosomes, most of them are symmetric. These chromosomes are normally originated de novo and are associated with mild to severe intellectual disability but not with physical abnormalities. We report on a patient with an SMC studied using classical and molecular cytogenetic procedures (G and C banding, NOR staining, painting and centromeric fluorescent in situ hybridization (FISH), BAC-FISH, and SKY). The MLPA technique and DNA polymorphic markers were used in order to identify its parental origin. The marker chromosome, monosatellited and monocentric, was found to be

Research paper thumbnail of Cytogenomic Diagnosis of Congenital Heart Diseases

Chromosome Research, 2013

Research paper thumbnail of Multi-gene panel testing improves diagnosis in Brazilian patients with Early-Onset Epilepsy

Research paper thumbnail of The role of CNVs in molecular mechanisms for rearrangements in 22q11.2 region diseases

Research paper thumbnail of 2 Deletion in Patients with Conotruncal Heart Defect and del 22 q Syndrome Phenotype

Results: Cytogenetic analysis by G-banding revealed a normal karyotype in all patients except one... more Results: Cytogenetic analysis by G-banding revealed a normal karyotype in all patients except one who presented a 47,XX,+idic(22)(q11.2) karyotype. Using molecular techniques, a deletion was observed in 25% of the patients, all exhibiting a 22q11.2 deletion syndrome phenotype. In none of the cases the deletion was inherited from the parents. The frequency of 22q11.2 deletion was higher in patients with the clinical spectrum of the 22q11.2 deletion syndrome than in patients with isolated conotruncal heart defect.

Research paper thumbnail of Cytogenomic Changes in Sporadic Colorectal Cancer and Surrounding Nonneoplastic Tissues: The Relevance of Subtelomeric Copy Number Variations

The purpose of this study was to investigate the relevance of subtelomeric cytogenomic changes in... more The purpose of this study was to investigate the relevance of subtelomeric cytogenomic changes in patients with sporadic colorectal cancer (CRC) using multiplex ligation-dependent probe amplification (MLPA) and single nucleotide polymorphism arrays. The results revealed pathogenic genomic alterations in the TNFRS18 (1p), CHL1 (3p), TRIML2 (4q), FBXO25 (8p), NKX3-1 (8p), RECQL4 (8q), DOCK8 (9p), ZMYND11 (10p), KDM5A (12p), PSPC1 (13q), ADPRTL2 (14q), MTA1 (14q), DECR2 (16p), GAS8 (16q), THOC1 (18p), CTDP1 (18q), SOX12 (20p), ADRM1 (20q), UCKL1 (20q), OPRL1 (20q), IL17RA (22q), and SYBL1 (Xq) genes. We detected copy number variations (CNVs) with frequencies greater than 40% in the probes located in 20q, which contains very important genes in the study of tumors. These findings showed instability in the tumor genome and altered regions associated with cell migration, transcription activation, apoptosis, and immune system deregulation. Unexpectedly, we detected concomitant pathogenic CN...

Research paper thumbnail of Case of 15q26-qter deletion associated with a Prader-Willi phenotype

European Journal of Medical Genetics, 2020

This is a PDF file of an article that has undergone enhancements after acceptance, such as the ad... more This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

Research paper thumbnail of Gene expression profile suggesting immunological dysregulation in two Brazilian Bloom's syndrome cases

Molecular Genetics & Genomic Medicine, 2020

This is an open access article under the terms of the Creative Commons Attribution License, which... more This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Research paper thumbnail of Clinical features of collagen VI-related dystrophies: A large Brazilian cohort

Clinical Neurology and Neurosurgery, 2020

Research paper thumbnail of The molecular landscape of osteogenesis imperfecta in a Brazilian tertiary service cohort

Osteoporosis International, 2020

We have sought the molecular diagnosis of OI in 38 Brazilian cases through targeted sequencing of... more We have sought the molecular diagnosis of OI in 38 Brazilian cases through targeted sequencing of 15 candidate genes. While 71% had type 1 collagen-related OI, defects in FKBP10, PLOD2 and SERPINF1, and a potential digenic P3H1/ WNT1 interaction were prominent causes of OI in this underrepresented population. Introduction Defects in type 1 collagen reportedly account for 85-90% of osteogenesis imperfecta (OI) cases, but most available molecular data has derived from Sanger sequencing-based approaches in developed countries. Massively parallel sequencing (MPS) allows for systematic and comprehensive analysis of OI genes simultaneously. Our objective was to obtain the molecular diagnosis of OI in a single Brazilian tertiary center cohort. Methods Forty-nine individuals (84% adults) with a clinical diagnosis of OI, corresponding to 30 sporadic and 8 familial cases, were studied. Sixty-three percent had moderate to severe OI, and consanguinity was common (26%). Coding regions and 25-bp boundaries of 15 OI genes (COL1A1, COL1A2, IFITM5 [plus 5′UTR],

Research paper thumbnail of Abstract B13: BLM, FOXO3, FOXK2, FOXM1, FOXR1 genes as therapeutic targets to neuroblastoma

Clinical Cancer Research, 2018

Due to heterogeneity of the neuroblastoma (NB) tumor, next-generation personalized medicine may i... more Due to heterogeneity of the neuroblastoma (NB) tumor, next-generation personalized medicine may identify therapeutic targets. Gene expression alterations of BLM (Bloom Syndrome RecQ Like Helicase) and FOX (Forkhead-box) family have been associated with an increased risk for cancer and resistance to chemotherapy drugs. Considering the potential implication of these genes on the clinical management of NB, we correlated clinical parameters, such as survival and treatments with genetic profiles of 11 NB patients stage 3 and 4 with MYCN-amplified (4 patients) or MYCN-non-amplified (7 patients) and one patient stage 2B and MYCN-non-amplified. Patients were treated with doxorubicin, etoposide, topotecan, cyclophosphamide, vincristine, and carboplatin. Targeted DNA sequencing, methylation array, and mRNA expression were performed on tumor and blood peripheral of these patients. Multiplex ligation-dependent probe amplification (MLPA). All variants considered important were validated by Sange...

Research paper thumbnail of Evaluation of Gene Expression in Early Substance Abuse

European Neuropsychopharmacology, 2019

Research paper thumbnail of Deletion of RUNX1 exons 1 and 2 associated with familial platelet disorder with propensity to acute myeloid leukemia

Cancer genetics, Apr 1, 2018

Familial platelet disorder with propensity to acute myeloid leukemia (FPD/AML) associated with RU... more Familial platelet disorder with propensity to acute myeloid leukemia (FPD/AML) associated with RUNX1 mutations is an autosomal dominant disorder included in the group of the myeloid neoplasms with germ line predisposition. We describe two brothers who were diagnosed with hematological malignancies (one with AML and the other with T-cell lymphoblastic lymphoma). There was a history of leukemia in the paternal family and two of their siblings presented with low platelet counts and no history of significant bleeding. A microdeletion encompassing exons 1-2 of RUNX1 (outside the cluster region of the Runt Homology domain and the transactivation domain) was detected in six family members using array-CGH and MLPA validation. A low platelet count was not present in all deletion carriers and, therefore, it should not be used as an indication for screening in suspected families and family members.

Research paper thumbnail of Duplication 9p and their implication to phenotype

BMC medical genetics, Jan 20, 2014

BackgroundTrisomy 9p is one of the most common partial trisomies found in newborns. We report the... more BackgroundTrisomy 9p is one of the most common partial trisomies found in newborns. We report the clinical features and cytogenomic findings in five patients with different chromosome rearrangements resulting in complete 9p duplication, three of them involving 9p centromere alterations.MethodsThe rearrangements in the patients were characterized by G-banding, SNP-array and fluorescent in situ hybridization (FISH) with different probes.ResultsTwo patients presented de novo dicentric chromosomes: der(9;15)t(9;15)(p11.2;p13) and der(9;21)t(9;21)(p13.1;p13.1). One patient presented two concomitant rearranged chromosomes: a der(12)t(9;12)(q21.13;p13.33) and an psu i(9)(p10) which showed FISH centromeric signal smaller than in the normal chromosome 9. Besides the duplication 9p24.3p13.1, array revealed a 7.3 Mb deletion in 9q13q21.13 in this patient. The break in the psu i(9)(p10) probably occurred in the centromere resulting in a smaller centromere and with part of the 9q translocated to...

Research paper thumbnail of Subtelomeric rearrangements and copy number variations in people with intellectual disabilities

Journal of Intellectual Disability Research, 2010

Background The most prevalent type of structural variation in the human genome is represented by ... more Background The most prevalent type of structural variation in the human genome is represented by copy number variations that can affect transcription levels, sequence, structure and function of genes. Method In the present study, we used the multiplex ligation-dependent probe amplification (MLPA) technique and quantitative PCR for the detection of copy number variation in 132 intellectually disabled male patients with normal karyotypes and negative fragile-X-testing. Results Ten of these patients (7.6%) showed copy number variation in the subtelomeric regions, including deletions and duplications. Discussion Duplications of the SECTM1 gene, located at 17q25.3, and of the FLJ22115 gene, located at 20p13, could be associated with phenotype alterations. This study highlights the relevance in the aetiology of intellectual disability of subtelomeric rearrangements that can be screened by MLPA and other molecular techniques.

Research paper thumbnail of Wide Clinical Variability in Cat Eye Syndrome Patients: Four Non-Related Patients and Three Patients from the Same Family

Cytogenetic and Genome Research, 2012

A small supernumerary marker chromosome (sSMC) derived from chromosome 22 is a relatively common ... more A small supernumerary marker chromosome (sSMC) derived from chromosome 22 is a relatively common cytogenetic finding. This sSMC typically results in tetrasomy for a chromosomal region that spans the chromosome 22p arm and the proximal 2 Mb of 22q11.21. Using classical cytogenetics, fluorescence in situ hybridization, multiplex ligation-dependent probe amplification, and array techniques, 7 patients with sSMCs derived from chromosome 22 were studied: 4 non-related and 3 from the same family (mother, daughter, and son). The sSMCs in all patients were dicentric and bisatellited chromosomes with breakpoints in the chromosome 22 low-copy repeat A region, resulting in cat eye syndrome (CES) due to chromosome 22 partial tetrasomy 22pter→q11.2 including the cat eye chromosome region. Although all subjects presented the same chromosomal abnormality, they showed a wide range of phenotypic differences, even in the 3 patients from the same family. There are no previous reports of CES occurring ...

Research paper thumbnail of Progression of Type 1 Diabetes: Circulating MicroRNA Expression Profiles Changes from Preclinical to Overt Disease

Journal of Immunology Research

Aims/Hypothesis. The role of microRNAs (miRNAs) in type 1 diabetes (T1D) pathogenesis and progres... more Aims/Hypothesis. The role of microRNAs (miRNAs) in type 1 diabetes (T1D) pathogenesis and progression has been described but remains elusive. Objectives. To evaluate the potential biological involvement of miRNA expression in the immune response and beta cell function in T1D. Methods.We screened 377 serum miRNAs of 110 subjects divided into four groups: healthy individuals (control group) and patients at different stages of T1D progression, from the initial immunological manifestation presenting islet autoantibodies (AbP group) until partial and strong beta cell damage in the recent (recent T1D group) and long-term T1D, with 2 to 5 years of disease (T1D 2-5y group).Results. The results revealed 69 differentially expressed miRNAs (DEMs) in relation to controls. Several miRNAs were correlated with islet autoantibodies (IA2A, GADA, and Znt8A), age, and C-peptide levels, mainly from AbP, and recent T1D groups pointing these miRNAs as relevant to T1D pathogenesis and progression. Several...

Research paper thumbnail of Cardiovascular findings in the Williams-Beuren syndrome

American Heart Journal, 1987

Research paper thumbnail of Genetic analysis of products of conception. Should we abandon classic karyotyping methodology?

Einstein (São Paulo)

Comparar os resultados obtidos pela metodologia clássica e molecular na análise de produtos de co... more Comparar os resultados obtidos pela metodologia clássica e molecular na análise de produtos de concepção, além das vantagens e desvantagens de cada método. Métodos: Análise retrospectiva não randomizada dos resultados obtidos a partir de amostras de produto de concepção submetidas à avaliação genética, de 2012 a 2017. As análises foram realizadas por citogenética clássica e/ou análise cromossômica de microarray ou arrays. Resultados: Quarenta amostras foram analisadas por citogenética, das quais 10% não apresentaram crescimento celular, 50% apresentaram resultados normais, e 40% apresentaram anormalidades. Dos 41 casos encaminhados para análise por array, não foi possível obter resultados em 7,3%, 39,5% eram normais, e 60,5% apresentavam alterações. Não houve diferença estatística entre os resultados (p=0,89). A maioria dos resultados anormais foi observada até a nona semana de gestação. Uma perda fetal mais tardia foi observada na 28ª semana de gestação, com cariótipo 46,XX,del(15) (q26.2-qter). Os números observados corroboraram a literatura mundial. Conclusão: As técnicas de citogenética clássica e análise por array mostraram resultados comparáveis no tipo de alteração observada. O array é preferível à cultura de células em abortos tardios, enquanto a citogenética é mais capaz de mostrar poliploidias. Ambos têm as mesmas taxas de falha de crescimento quando o tecido do produto de concepção não é coletado adequadamente.

Research paper thumbnail of Fetal gastroschisis: Maternal and fetal methylation profile

Prenatal Diagnosis, 2021

The purpose of this study was to describe the genomic deoxyribonucleic acid (DNA) methylation pro... more The purpose of this study was to describe the genomic deoxyribonucleic acid (DNA) methylation profile in fetuses with gastroschisis, determine whether the profile was inherited, and investigate any possible correlations with maternal risk factors.

Research paper thumbnail of CLINICAL REPORT A Rare Case of Trisomy 15pter-q21.2 Due to a De Novo

be associated with an abnormal phenotype, depending on the presence of euchromatin, on their chro... more be associated with an abnormal phenotype, depending on the presence of euchromatin, on their chromosomal origin and whether they are inherited. Over 80 % of sSMCs are derived from acrocentric chromosomes and half of them include the short arm of chromosome 15. Generally, they appear as bisatellited isodicentric marker chromosomes, most of them are symmetric. These chromosomes are normally originated de novo and are associated with mild to severe intellectual disability but not with physical abnormalities. We report on a patient with an SMC studied using classical and molecular cytogenetic procedures (G and C banding, NOR staining, painting and centromeric fluorescent in situ hybridization (FISH), BAC-FISH, and SKY). The MLPA technique and DNA polymorphic markers were used in order to identify its parental origin. The marker chromosome, monosatellited and monocentric, was found to be

Research paper thumbnail of Cytogenomic Diagnosis of Congenital Heart Diseases

Chromosome Research, 2013

Research paper thumbnail of Multi-gene panel testing improves diagnosis in Brazilian patients with Early-Onset Epilepsy

Research paper thumbnail of The role of CNVs in molecular mechanisms for rearrangements in 22q11.2 region diseases

Research paper thumbnail of 2 Deletion in Patients with Conotruncal Heart Defect and del 22 q Syndrome Phenotype

Results: Cytogenetic analysis by G-banding revealed a normal karyotype in all patients except one... more Results: Cytogenetic analysis by G-banding revealed a normal karyotype in all patients except one who presented a 47,XX,+idic(22)(q11.2) karyotype. Using molecular techniques, a deletion was observed in 25% of the patients, all exhibiting a 22q11.2 deletion syndrome phenotype. In none of the cases the deletion was inherited from the parents. The frequency of 22q11.2 deletion was higher in patients with the clinical spectrum of the 22q11.2 deletion syndrome than in patients with isolated conotruncal heart defect.

Research paper thumbnail of Cytogenomic Changes in Sporadic Colorectal Cancer and Surrounding Nonneoplastic Tissues: The Relevance of Subtelomeric Copy Number Variations

The purpose of this study was to investigate the relevance of subtelomeric cytogenomic changes in... more The purpose of this study was to investigate the relevance of subtelomeric cytogenomic changes in patients with sporadic colorectal cancer (CRC) using multiplex ligation-dependent probe amplification (MLPA) and single nucleotide polymorphism arrays. The results revealed pathogenic genomic alterations in the TNFRS18 (1p), CHL1 (3p), TRIML2 (4q), FBXO25 (8p), NKX3-1 (8p), RECQL4 (8q), DOCK8 (9p), ZMYND11 (10p), KDM5A (12p), PSPC1 (13q), ADPRTL2 (14q), MTA1 (14q), DECR2 (16p), GAS8 (16q), THOC1 (18p), CTDP1 (18q), SOX12 (20p), ADRM1 (20q), UCKL1 (20q), OPRL1 (20q), IL17RA (22q), and SYBL1 (Xq) genes. We detected copy number variations (CNVs) with frequencies greater than 40% in the probes located in 20q, which contains very important genes in the study of tumors. These findings showed instability in the tumor genome and altered regions associated with cell migration, transcription activation, apoptosis, and immune system deregulation. Unexpectedly, we detected concomitant pathogenic CN...

Research paper thumbnail of Case of 15q26-qter deletion associated with a Prader-Willi phenotype

European Journal of Medical Genetics, 2020

This is a PDF file of an article that has undergone enhancements after acceptance, such as the ad... more This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

Research paper thumbnail of Gene expression profile suggesting immunological dysregulation in two Brazilian Bloom's syndrome cases

Molecular Genetics & Genomic Medicine, 2020

This is an open access article under the terms of the Creative Commons Attribution License, which... more This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Research paper thumbnail of Clinical features of collagen VI-related dystrophies: A large Brazilian cohort

Clinical Neurology and Neurosurgery, 2020

Research paper thumbnail of The molecular landscape of osteogenesis imperfecta in a Brazilian tertiary service cohort

Osteoporosis International, 2020

We have sought the molecular diagnosis of OI in 38 Brazilian cases through targeted sequencing of... more We have sought the molecular diagnosis of OI in 38 Brazilian cases through targeted sequencing of 15 candidate genes. While 71% had type 1 collagen-related OI, defects in FKBP10, PLOD2 and SERPINF1, and a potential digenic P3H1/ WNT1 interaction were prominent causes of OI in this underrepresented population. Introduction Defects in type 1 collagen reportedly account for 85-90% of osteogenesis imperfecta (OI) cases, but most available molecular data has derived from Sanger sequencing-based approaches in developed countries. Massively parallel sequencing (MPS) allows for systematic and comprehensive analysis of OI genes simultaneously. Our objective was to obtain the molecular diagnosis of OI in a single Brazilian tertiary center cohort. Methods Forty-nine individuals (84% adults) with a clinical diagnosis of OI, corresponding to 30 sporadic and 8 familial cases, were studied. Sixty-three percent had moderate to severe OI, and consanguinity was common (26%). Coding regions and 25-bp boundaries of 15 OI genes (COL1A1, COL1A2, IFITM5 [plus 5′UTR],

Research paper thumbnail of Abstract B13: BLM, FOXO3, FOXK2, FOXM1, FOXR1 genes as therapeutic targets to neuroblastoma

Clinical Cancer Research, 2018

Due to heterogeneity of the neuroblastoma (NB) tumor, next-generation personalized medicine may i... more Due to heterogeneity of the neuroblastoma (NB) tumor, next-generation personalized medicine may identify therapeutic targets. Gene expression alterations of BLM (Bloom Syndrome RecQ Like Helicase) and FOX (Forkhead-box) family have been associated with an increased risk for cancer and resistance to chemotherapy drugs. Considering the potential implication of these genes on the clinical management of NB, we correlated clinical parameters, such as survival and treatments with genetic profiles of 11 NB patients stage 3 and 4 with MYCN-amplified (4 patients) or MYCN-non-amplified (7 patients) and one patient stage 2B and MYCN-non-amplified. Patients were treated with doxorubicin, etoposide, topotecan, cyclophosphamide, vincristine, and carboplatin. Targeted DNA sequencing, methylation array, and mRNA expression were performed on tumor and blood peripheral of these patients. Multiplex ligation-dependent probe amplification (MLPA). All variants considered important were validated by Sange...

Research paper thumbnail of Evaluation of Gene Expression in Early Substance Abuse

European Neuropsychopharmacology, 2019

Research paper thumbnail of Deletion of RUNX1 exons 1 and 2 associated with familial platelet disorder with propensity to acute myeloid leukemia

Cancer genetics, Apr 1, 2018

Familial platelet disorder with propensity to acute myeloid leukemia (FPD/AML) associated with RU... more Familial platelet disorder with propensity to acute myeloid leukemia (FPD/AML) associated with RUNX1 mutations is an autosomal dominant disorder included in the group of the myeloid neoplasms with germ line predisposition. We describe two brothers who were diagnosed with hematological malignancies (one with AML and the other with T-cell lymphoblastic lymphoma). There was a history of leukemia in the paternal family and two of their siblings presented with low platelet counts and no history of significant bleeding. A microdeletion encompassing exons 1-2 of RUNX1 (outside the cluster region of the Runt Homology domain and the transactivation domain) was detected in six family members using array-CGH and MLPA validation. A low platelet count was not present in all deletion carriers and, therefore, it should not be used as an indication for screening in suspected families and family members.

Research paper thumbnail of Duplication 9p and their implication to phenotype

BMC medical genetics, Jan 20, 2014

BackgroundTrisomy 9p is one of the most common partial trisomies found in newborns. We report the... more BackgroundTrisomy 9p is one of the most common partial trisomies found in newborns. We report the clinical features and cytogenomic findings in five patients with different chromosome rearrangements resulting in complete 9p duplication, three of them involving 9p centromere alterations.MethodsThe rearrangements in the patients were characterized by G-banding, SNP-array and fluorescent in situ hybridization (FISH) with different probes.ResultsTwo patients presented de novo dicentric chromosomes: der(9;15)t(9;15)(p11.2;p13) and der(9;21)t(9;21)(p13.1;p13.1). One patient presented two concomitant rearranged chromosomes: a der(12)t(9;12)(q21.13;p13.33) and an psu i(9)(p10) which showed FISH centromeric signal smaller than in the normal chromosome 9. Besides the duplication 9p24.3p13.1, array revealed a 7.3 Mb deletion in 9q13q21.13 in this patient. The break in the psu i(9)(p10) probably occurred in the centromere resulting in a smaller centromere and with part of the 9q translocated to...

Research paper thumbnail of Subtelomeric rearrangements and copy number variations in people with intellectual disabilities

Journal of Intellectual Disability Research, 2010

Background The most prevalent type of structural variation in the human genome is represented by ... more Background The most prevalent type of structural variation in the human genome is represented by copy number variations that can affect transcription levels, sequence, structure and function of genes. Method In the present study, we used the multiplex ligation-dependent probe amplification (MLPA) technique and quantitative PCR for the detection of copy number variation in 132 intellectually disabled male patients with normal karyotypes and negative fragile-X-testing. Results Ten of these patients (7.6%) showed copy number variation in the subtelomeric regions, including deletions and duplications. Discussion Duplications of the SECTM1 gene, located at 17q25.3, and of the FLJ22115 gene, located at 20p13, could be associated with phenotype alterations. This study highlights the relevance in the aetiology of intellectual disability of subtelomeric rearrangements that can be screened by MLPA and other molecular techniques.

Research paper thumbnail of Wide Clinical Variability in Cat Eye Syndrome Patients: Four Non-Related Patients and Three Patients from the Same Family

Cytogenetic and Genome Research, 2012

A small supernumerary marker chromosome (sSMC) derived from chromosome 22 is a relatively common ... more A small supernumerary marker chromosome (sSMC) derived from chromosome 22 is a relatively common cytogenetic finding. This sSMC typically results in tetrasomy for a chromosomal region that spans the chromosome 22p arm and the proximal 2 Mb of 22q11.21. Using classical cytogenetics, fluorescence in situ hybridization, multiplex ligation-dependent probe amplification, and array techniques, 7 patients with sSMCs derived from chromosome 22 were studied: 4 non-related and 3 from the same family (mother, daughter, and son). The sSMCs in all patients were dicentric and bisatellited chromosomes with breakpoints in the chromosome 22 low-copy repeat A region, resulting in cat eye syndrome (CES) due to chromosome 22 partial tetrasomy 22pter→q11.2 including the cat eye chromosome region. Although all subjects presented the same chromosomal abnormality, they showed a wide range of phenotypic differences, even in the 3 patients from the same family. There are no previous reports of CES occurring ...

Research paper thumbnail of Progression of Type 1 Diabetes: Circulating MicroRNA Expression Profiles Changes from Preclinical to Overt Disease

Journal of Immunology Research

Aims/Hypothesis. The role of microRNAs (miRNAs) in type 1 diabetes (T1D) pathogenesis and progres... more Aims/Hypothesis. The role of microRNAs (miRNAs) in type 1 diabetes (T1D) pathogenesis and progression has been described but remains elusive. Objectives. To evaluate the potential biological involvement of miRNA expression in the immune response and beta cell function in T1D. Methods.We screened 377 serum miRNAs of 110 subjects divided into four groups: healthy individuals (control group) and patients at different stages of T1D progression, from the initial immunological manifestation presenting islet autoantibodies (AbP group) until partial and strong beta cell damage in the recent (recent T1D group) and long-term T1D, with 2 to 5 years of disease (T1D 2-5y group).Results. The results revealed 69 differentially expressed miRNAs (DEMs) in relation to controls. Several miRNAs were correlated with islet autoantibodies (IA2A, GADA, and Znt8A), age, and C-peptide levels, mainly from AbP, and recent T1D groups pointing these miRNAs as relevant to T1D pathogenesis and progression. Several...

Research paper thumbnail of Cardiovascular findings in the Williams-Beuren syndrome

American Heart Journal, 1987