Clinical Phenotype and Genetic Analysis of a Family with 17q12 Microdeletion Syndrome
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE296489 | GEO | 2026/05/07
REPOSITORIES: GEO
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Project description:The 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 lead to a wide spectrum of clinical manifestations. Terminal 12p deletion represents one of the rarest subtelomeric imbalance, patients with distal monosomy 12p present different phenotypes ranging from muscular hypotonia to autism spectrum disorders. Here we report a prenatal diagnosis of a male fetus presenting ultrasounds 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 has rarely been reported together. As the 12p13.33 microdeletion in the father was associated only to muscular hypotonia and joint laxity, involvement of terminal 12p deletions in fetus clinical features was not possible to verify in prenatal period. This report may provide a reference for prenatal diagnosis and genetic counseling in patients who have prenatal diagnosis of 3q13q21.2 deletions and 12p13.33 microdeletion.
2022-11-10 | E-MTAB-12413 | biostudies-arrayexpress
Project description:The study presents three cases of patients with deletions within 16p11.2 regions. Every child had characteristic craniofacial dysmorphic features and hand or feet abnormalities. The first proband had additionally obesity, epilepsy, moderate intellectual disability, aphasia, motor delay, hyperinsulinism and café au lait spots. The second proband suffered from cardiac, pulmonary and hematological problems. The third proband had motor delay, bronchial asthma and umbilical hernia. Although each patient presented characteristic features of the syndrome, children differed in clinical pictures among themselves. The genetic diagnosis of the 16p11.2 deletion syndrome was made in children at different age, based on the multiplex ligation probe-dependent amplification (MLPA) analysis and/or microarrays methods. This study highlights the impact of the size of deleted regions, as they may affect the clinical picture of patients with 16p11.2 microdeletion syndrome. Reported cases indicates the key role of the interdisciplinary approach in 16p11.2 microdeletion syndrome diagnostics, as the care of patients with this deletion is based on regular health assessment and adjustment of the nervous system development therapy
2020-10-07 | GSE159129 | GEO
Project description:We designed a microarray to test at exonic resolution for genomic imbalance for genes representative of all known chromosomal microdeletion/microduplication syndromes, all known causative genes for ID, all known genes encoding glutamate receptors and their known encoding proteins and all known genes encoding proteins with epigenetic regulatory function. We found 36 de novo copy number variants affecting 35 children in this study. 167 trios, each comprising an affected child and both its normal parents were analyzed by conducting two comparative hybridizations; child vs. mother and child vs. father, and only selecting a CNV if it appeared in both hybridizations, i.e., was de novo. De novo CNVs were independantly validated using quantitative PCR.
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Project description:We identified a family with a novel chromosome 13 microdeletion associated with a syndromic form of corneal opacification. In order to determine which genes in/around the microdeletion were contributing to the constellation of phenotypes, a corneal epithelial sample was obtained during a superficial keratectomy of the proband's 9-year-old brother.
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Project description:We identified a novel homozygous 15q13.3 microdeletion in a young boy with a complex neurodevelopmental disorder characterized by severe cerebral visual impairment with additional signs of congenital stationary night blindness (CSNB), congenital hypotonia with areflexia, profound intellectual disability, and refractory epilepsy. The mechanisms by which the genes in the deleted region exert their effect are unclear. In this paper we probed the role of downstream effects of the deletions as a contributing mechanism to the molecular basis of the observed phenotype. We analyzed gene expression of lymphoblastoid cells derived from peripheral blood of the proband and his relatives to ascertain the relative effects of the homozygous and heterozygous deletions. The proband with 15q13.3 homozygous deletion and his parents with 15q13.3 heterozygous deletions described in our previous report 15 were evaluated using Affymetrix aCGH-244K arrays (build hg18). The aCGH data were validated by qPCR using primers specific to CHRNA7 as previously described. 15 The extended family and comparison subjects were also screened using the CHRNA7 primers. Immortalized lymphoblastoid lines were created from the proband, his mother, father, a paternal half sister, a paternal half brother, a paternal grandmother and two paternal great uncles. Three lymphoblastoid lines from age- and sex- matched normally developing comparison subjects with normal chromosomes were obtained from the Coriell cell repository [(AG14724 (8 yo), AG14948 (10 yo), AG14980 (9 yo)] were used for gene expression comparison with the proband. The samples from the father, mother and paternal grandmother with heterozygous 15q13.3 deletions were compared to samples from lymphoblastoid cells from adult male and female subjects respectively (normal copy number for 15q13.3 determined by qPCR).
2013-02-17 | E-GEOD-43583 | biostudies-arrayexpress
Project description:The cause of mental retardation in one-third to one-half of all affected individuals is unknown. Microscopically-detectable chromosomal abnormalities are the most frequent recognized cause, but gain or loss of chromosomal segments that are too small to be seen by conventional cytogenetic analysis has been found to be another important cause. Array-based methods offer a practical means of performing a high-resolution survey of the entire genome for submicroscopic copy number variants. We studied 100 children with idiopathic mental retardation and their parents using the Affymetrix GeneChip® Mapping 100K Assay and found de novo duplications as small as 1.1 Mb in three cases, de novo deletions as small as 178 kb in eight cases, and unsuspected mosaic trisomy 9 in another case. This technology can detect at least twice as many potentially pathogenic de novo copy number variants as conventional cytogenetic analysis in people with mental retardation. Experiment Overall Design: Using the Affymetrix GeneChip® Mapping 100K Assay we studied 100 trios that each included one child with idiopathic mental retardation (MR) and both of his/her unaffected biological parents. We also tested 10 unaffected siblings of the MR children from 10 of the above families. In addition, we analyzed 7 trios (child and both unaffected biological parents) as positive controls with previously identified chromosomal aberrations. Experiment Overall Design: Within each sample ID the four digit number refers to a family. Following this four digit family number, 'c' indicates child with MR, 'm' means unaffected mother, 'f' means unaffected father and 's' means unaffected sibling.
2008-06-21 | E-GEOD-7226 | biostudies-arrayexpress
Project description:Dysfunction of the thalamocortical pathway has been implicated in multiple psychiatric disorders, but mechanisms by which these defects emerge remain poorly understood. We explored this question in the context of the 22q11.2 microdeletion, which represents a significant genetic risk for schizophrenia, leveraging emerging technologies of in vitro brain organogenesis using chimeric brain organoids derived from human induced pluripotent stem cells. Here we show that the 22q11.2 microdeletion leads to transcriptional dysregulation in thalamic organoids that is enriched for psychiatric disease risk genes, including elevated expression of FOXP2, which represents the most significantly dysregulated transcription factor in glutamatergic neurons and astroctyes. In a co-culture model fusing thalamic and cortical organoids, we demonstrate that the 22q11.2 deletion mediates an overgrowth of thalamic axons via overexpression of FOXP2, which then subsequently mediates the overgrowth of reciprocal corticothalamic axons. Dysregulation of FOXP2 leads to downregulation of ROBO2, an axon repulsive receptor important for thalamocortical axon pathfinding, and knockdown of ROBO2 in control organoids phenocopies excessive outgrowth of thalamic axons. Together, our study suggests that early steps in thalamocortical pathway development may be dysregulated in a model of genetic risk for schizophrenia, and contribute to neural phenotypes in 22q11.2 microdeletion syndrome.
2024-02-22 | GSE245719 | GEO
Project description:Clinical and molecular characterization of patients with 16p11.2 microdeletion syndrome
| PRJNA667734 | ENA
Project description:Background: Despite of extensive research the genetic component of extremely low birth weight in newborns has remained obscure. Results: The aim of the case study was to identify candidate gene(s) causing extremely low birth weight (ELBW) in newborns and hypotrophy in infants. A four-member family was studied: mother, father and two ELBW-phenotype children. The studies were carried out due to the medical conditions of the second child at birth and post-partum: peculiar phenotype, micro-anomalies, recurrent infections, suspicion of autoimmune hepatitis, multifactorial encephalopathy, and suspicion of metabolic and chromosomal abnormalities. Whole genome single nucleotide polymorphism (SNP) genotyping array was used to investigate genomic rearrangements in both affected children using peripheral blood DNA samples. Whole blood transcriptome was assessed by using RNA sequencing (RNA-seq) in all four family members. RNA-seq identified a single gene – C14orf132 differentially expressed, with the level of the transcript significantly lower in blood samples of children. Copy number variant (CNV) analysis did not reveal any pathogenic CNVs in the region of C14orf132 gene of both affected children. Conclusion: We showed the importance of combining whole genome CNV and transcriptome analysis in identification of the candidate gene(s) in case studies. We propose the C14orf132 (chromosome 14 open reading frame 132) gene expression to be associated with the ELBW-phenotype. C14orf132 gene is a novel long non-coding RNA (lincRNA) with unknown function, which might be associated with the developmental delay through the altered gene expression Background: Despite of extensive research the genetic component of extremely low birth weight in newborns has remained obscure. Results: The aim of the case study was to identify candidate gene(s) causing extremely low birth weight (ELBW) in newborns and hypotrophy in infants. A four-member family was studied: mother, father and two ELBW-phenotype children. The studies were carried out due to the medical conditions of the second child at birth and post-partum: peculiar phenotype, micro-anomalies, recurrent infections, suspicion of autoimmune hepatitis, multifactorial encephalopathy, and suspicion of metabolic and chromosomal abnormalities. Whole genome single nucleotide polymorphism (SNP) genotyping array was used to investigate genomic rearrangements in both affected children using peripheral blood DNA samples. Whole blood transcriptome was assessed by using RNA sequencing (RNA-seq) in all four family members. RNA-seq identified a single gene – C14orf132 differentially expressed, with the level of the transcript significantly lower in blood samples of children. Copy number variant (CNV) analysis did not reveal any pathogenic CNVs in the region of C14orf132 gene of both affected children. Conclusion: We showed the importance of combining whole genome CNV and transcriptome analysis in identification of the candidate gene(s) in case studies. We propose the C14orf132 (chromosome 14 open reading frame 132) gene expression to be associated with the ELBW-phenotype. C14orf132 gene is a novel long non-coding RNA (lincRNA) with unknown function, which might be associated with the developmental delay through the altered gene expression Background: Despite of extensive research the genetic component of extremely low birth weight in newborns has remained obscure. Results: The aim of the case study was to identify candidate gene(s) causing extremely low birth weight (ELBW) in newborns and hypotrophy in infants. A four-member family was studied: mother, father and two ELBW-phenotype children. The studies were carried out due to the medical conditions of the second child at birth and post-partum: peculiar phenotype, micro-anomalies, recurrent infections, suspicion of autoimmune hepatitis, multifactorial encephalopathy, and suspicion of metabolic and chromosomal abnormalities. Whole genome single nucleotide polymorphism (SNP) genotyping array was used to investigate genomic rearrangements in both affected children using peripheral blood DNA samples. Whole blood transcriptome was assessed by using RNA sequencing (RNA-seq) in all four family members. RNA-seq identified a single gene – C14orf132 differentially expressed, with the level of the transcript significantly lower in blood samples of children. Copy number variant (CNV) analysis did not reveal any pathogenic CNVs in the region of C14orf132 gene of both affected children. Conclusion: We showed the importance of combining whole genome CNV and transcriptome analysis in identification of the candidate gene(s) in case studies. We propose the C14orf132 (chromosome 14 open reading frame 132) gene expression to be associated with the ELBW-phenotype. C14orf132 gene is a novel long non-coding RNA (lincRNA) with unknown function, which might be associated with the developmental delay through the altered gene expression. Background: Despite of extensive research the genetic component of extremely low birth weight in newborns has remained obscure. Results: The aim of the case study was to identify candidate gene(s) causing extremely low birth weight (ELBW) in newborns and hypotrophy in infants. A four-member family was studied: mother, father and two ELBW-phenotype children. The studies were carried out due to the medical conditions of the second child at birth and post-partum: peculiar phenotype, micro-anomalies, recurrent infections, suspicion of autoimmune hepatitis, multifactorial encephalopathy, and suspicion of metabolic and chromosomal abnormalities. Whole genome single nucleotide polymorphism (SNP) genotyping array was used to investigate genomic rearrangements in both affected children using peripheral blood DNA samples. Whole blood transcriptome was assessed by using RNA sequencing (RNA-seq) in all four family members. RNA-seq identified a single gene – C14orf132 differentially expressed, with the level of the transcript significantly lower in blood samples of children. Copy number variant (CNV) analysis did not reveal any pathogenic CNVs in the region of C14orf132 gene of both affected children. Conclusion: We showed the importance of combining whole genome CNV and transcriptome analysis in identification of the candidate gene(s) in case studies. We propose the C14orf132 (chromosome 14 open reading frame 132) gene expression to be associated with the ELBW-phenotype. C14orf132 gene is a novel long non-coding RNA (lincRNA) with unknown function, which might be associated with the developmental delay through the altered gene expression.
2016-08-01 | GSE85013 | GEO