Homo sapiens
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ABSTRACT:
PROVIDER: PRJNA100937 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:In this study we report a female patient with an interstitial duplication of a region (10q22-q23) which is rarely reported in the literature. We fine mapped the duplication with array CGH, which revealed an 18.6 Mb duplication at 10q22.2-q23.33. There were no other deletions or duplication at another chromosome region. The duplicated region includes 89 annotated genes. The main clinical features of the patient are microcephaly and congenital heart disease. These are likely to be caused by dosage effect of one or several genes in the duplicated region. Finding of similar phenotypes in the other patients with 10q11-q22 duplications and in two out of three patients with 10q22-q23 duplications, suggest presence of genes involved in the development of these features at 10q22. Most of the duplication cases were investigated only by conventional chromosome analyses and fine mapping of these duplications will help identifying candidate genes/regions. Keywords: Array CGH
2007-10-01 | GSE8090 | GEO
Project description:Here we describe an interstitial pure duplication of 19p13.3 that was initially considered as a de novo alteration, in a patient with intellectual disability studied by array-CGH. The finding of the same chromosomal alteration in a first-degree cousin of this patient led us to investigate the presence of insertional translocations. An intrachromosomal insertional translocation was found in at least three generations. Three intellectually disabled patients with the same duplication and multiples abortions among translocation carrier family members were found. A review of other published cases has allowed us to find three other cases with a similar pure duplication and some clinical findings present in all patients as intrauterine growth retardation, microcephaly, motor and speech delay, moderate to severe intellectual disability and dysmorphic features. These findings allow us to suggest the existence of a new microduplication syndrome in chromosomal region 19p13.3.
2014-05-22 | GSE57899 | GEO
Project description:Here we describe an interstitial pure duplication of 19p13.3 that was initially considered as a de novo alteration, in a patient with intellectual disability studied by array-CGH. The finding of the same chromosomal alteration in a first-degree cousin of this patient led us to investigate the presence of insertional translocations. An intrachromosomal insertional translocation was found in at least three generations. Three intellectually disabled patients with the same duplication and multiples abortions among translocation carrier family members were found. A review of other published cases has allowed us to find three other cases with a similar pure duplication and some clinical findings present in all patients as intrauterine growth retardation, microcephaly, motor and speech delay, moderate to severe intellectual disability and dysmorphic features. These findings allow us to suggest the existence of a new microduplication syndrome in chromosomal region 19p13.3. Whole genome array-CGH was performed on Agilent oligo-chip 44K (human genome CGH microarray G4410B from Agilent Technologies, Palo Alto, CA) as recommended. The patientsM-bM-^@M-^Y DNA samples were tested against a pool of 10 sex-matched normal DNA samples, all of them (patients and normal controls) from our geographical area. Scanned images were quantified using Agilent Feature Extraction Software (v9.0). The results were analyzed using Agilent Genomic Workbench software. Annotations have been obtained from UCSC (http://genome.ucsc.edu) based on human genome build GRCh37/hg19.
2014-05-22 | E-GEOD-57899 | biostudies-arrayexpress
Project description:Ongoing studies using genomic microarrays and next-generation sequencing have demonstrated that the genetic contributions to cardiovascular diseases have been significantly ignored in the past. The aim of this study was to identify rare copy number variants in individuals with congenital pulmonary atresia (PA). Based on the hypothesis that rare structural variants encompassing key genes play an important role in heart development in PA patients, we performed high-resolution genome-wide microarrays for copy number variations (CNVs) in 82 PA patient-parent trios and 189 controls with an Illumina SNP array platform. CNVs were identified in 17/82 patients (20.7%), and eight of these CNVs (9.8%) are considered potentially pathogenic. Five de novo CNVs occurred at two known congenital heart disease (CHD) loci (16p13.1 and 22q11.2). Two de novo CNVs that may affect folate and vitamin B12 metabolism were identified for the first time. A de novo 1-Mb deletion at 17p13.2 may represent a rare genomic disorder that involves mild intellectual disability and associated facial features. high-resolution genome-wide microarrays for copy number variations (CNVs) in 82 PA patient-parent trios and 189 controls with an Illumina SNP array platform. Only 21 samples with potentially pathogenic CNVs are included in this records
2014-04-02 | E-GEOD-56422 | biostudies-arrayexpress
Project description:Ongoing studies using genomic microarrays and next-generation sequencing have demonstrated that the genetic contributions to cardiovascular diseases have been significantly ignored in the past. The aim of this study was to identify rare copy number variants in individuals with congenital pulmonary atresia (PA). Based on the hypothesis that rare structural variants encompassing key genes play an important role in heart development in PA patients, we performed high-resolution genome-wide microarrays for copy number variations (CNVs) in 82 PA patient-parent trios and 189 controls with an Illumina SNP array platform. CNVs were identified in 17/82 patients (20.7%), and eight of these CNVs (9.8%) are considered potentially pathogenic. Five de novo CNVs occurred at two known congenital heart disease (CHD) loci (16p13.1 and 22q11.2). Two de novo CNVs that may affect folate and vitamin B12 metabolism were identified for the first time. A de novo 1-Mb deletion at 17p13.2 may represent a rare genomic disorder that involves mild intellectual disability and associated facial features.
2014-04-02 | GSE56422 | GEO
Project description:Chromothripsis represents an extreme class of complex chromosome rearrangements (CCRs) with major effects on chromosomal architecture. Although recent studies have associated chromothripsis with congenital abnormalities, the incidence and pathogenic effects of this phenomenon require further investigation. Here, we analyzed the genomes of three families in which chromothripsis rearrangements were transmitted from a mother to her child. The chromothripsis in the mothers resulted in completely balanced rearrangements involving 8-23 breakpoint junctions across 3-5 chromosomes. Two mothers did not show any phenotypic malformations, although 3-13 protein coding genes were affected by breakpoints. Unbalanced but stable transmission of a subset of the derivative chromosomes caused apparently de novo complex copy number changes in two children. This resulted in gene dosage changes, which are likely responsible for their severe congenital phenotypes. In contrast, one child with severe congenital disease, carried all three chromothripsis chromosomes from his healthy mother, but one of the chromosomes acquired de novo rearrangements leading to copy number changes. These results show that the human genome can tolerate extreme reshuffling of chromosomal architecture, including breakage of multiple protein coding genes, without noticeable phenotypic effects. The presence of chromothripsis in healthy individuals strongly affects reproduction and is expected to substantially increase the risk of spontaneous abortions and severe congenital disease. We analyzed one patient-parent-mother's parents quintet (case 1) and a patient-siblings-parent quintet (case 2) with Illumina beadchip arrays and one patient-parent trio (case 3) to test for (de novo) copy number variants and to analyze the parental origin of the complex rearrangements in these patients. Here, we analyzed one patient-parent-mother's parents quintet to test for (de novo) copy number variants and to analyze the parental origin of the complex rearrangements in these patients.
2015-01-31 | E-GEOD-65451 | biostudies-arrayexpress
Project description:Chromothripsis represents an extreme class of complex chromosome rearrangements (CCRs) with major effects on chromosomal architecture. Although recent studies have associated chromothripsis with congenital abnormalities, the incidence and pathogenic effects of this phenomenon require further investigation. Here, we analyzed the genomes of three families in which chromothripsis rearrangements were transmitted from a mother to her child. The chromothripsis in the mothers resulted in completely balanced rearrangements involving 8-23 breakpoint junctions across 3-5 chromosomes. Two mothers did not show any phenotypic malformations, although 3-13 protein coding genes were affected by breakpoints. Unbalanced but stable transmission of a subset of the derivative chromosomes caused apparently de novo complex copy number changes in two children. This resulted in gene dosage changes, which are likely responsible for their severe congenital phenotypes. In contrast, one child with severe congenital disease, carried all three chromothripsis chromosomes from his healthy mother, but one of the chromosomes acquired de novo rearrangements leading to copy number changes. These results show that the human genome can tolerate extreme reshuffling of chromosomal architecture, including breakage of multiple protein coding genes, without noticeable phenotypic effects. The presence of chromothripsis in healthy individuals strongly affects reproduction and is expected to substantially increase the risk of spontaneous abortions and severe congenital disease. We analyzed one patient-parent-mother's parents quintet (case 1) and a patient-siblings-parent quintet (case 2) with Illumina beadchip arrays and one patient-parent trio (case 3) to test for (de novo) copy number variants and to analyze the parental origin of the complex rearrangements in these patients. This study represents one child-parent trio (case 3) test for (de novo) copy number variants in the child.
2015-01-31 | E-GEOD-65453 | biostudies-arrayexpress
Project description:To determine the pathogenesis of a patient born with congenital heart defects, who had appeared normal in prenatal screening. In routine prenatal screening, G-banding was performed to analyse the karyotypes of the family and fluorescence in situ hybridization was used to investigate the 22q11.2 deletion in the fetus. After birth, the child was found to be suffering from heart defects by transthoracic echocardiography. In the following study, sequencing was used to search for potential mutations in pivotal genes. SNP-array was employed for fine mapping of the aberrant region and quantitative real-time PCR was used to confirm the results. Furthermore, other patients with a similar phenotype were screened for the same genetic variations. To compare with a control, these variations were also assessed in the general population.
2014-06-27 | E-GEOD-48386 | biostudies-arrayexpress
Project description:Chromothripsis represents an extreme class of complex chromosome rearrangements (CCRs) with major effects on chromosomal architecture. Although recent studies have associated chromothripsis with congenital abnormalities, the incidence and pathogenic effects of this phenomenon require further investigation. Here, we analyzed the genomes of three families in which chromothripsis rearrangements were transmitted from a female carrier to her child. The chromothripsis in the carriers resulted in completely balanced rearrangements involving 8-23 breakpoint junctions across 3-5 chromosomes. Two carriers did not show any phenotypic malformations, although 3-13 protein coding genes were affected by breakpoints. Unbalanced but stable transmission of a subset of the derivative chromosomes caused apparently de novo complex copy number changes in two children. This resulted in gene dosage changes, which are likely responsible for their severe congenital phenotypes. In contrast, one patient with severe congenital disease, carried all three chromothripsis chromosomes from his healthy mother, but one of the chromosomes acquired de novo rearrangements leading to copy number changes. These results show that the human genome can tolerate extreme reshuffling of chromosomal architecture, including breakage of multiple protein coding genes, without noticeable phenotypic effects. The presence of chromothripsis in healthy carriers strongly affects reproduction and is expected to substantially increase the risk of spontaneous abortions and severe congenital disease. We analyzed one patient-parent-mother's parents quintet (case 1) and a patient-siblings-parent quintet (case 2) with Illumina beadchip arrays and one patient-parent trio (case 3) to test for (de novo) copy number variants and to analyze the parental origin of the complex rearrangements in these patients. For case 2, the mother and patient's SNP array data was previously submitted [GSE37906]. aCGH data for case 3 is submitted seperately.
2015-01-31 | E-GEOD-65452 | biostudies-arrayexpress
Project description:An increasing number of genes involved in chromatin structure and epigenetic regulation has been implicated in a variety of developmental disorders, often including intellectual disability. By trio exome sequencing and subsequent mutational screening we now identified two de novo frameshift mutations and one de novo missense mutation in the CTCF gene in individuals with intellectual disability, microcephaly and growth retardation. Furthermore, a patient with a larger deletion including CTCF was identified. CTCF (CCCTC-binding factor) is one of the most important chromatin organizers in vertebrates and is involved in various chromatin regulation processes such as higher order of chromatin organization, enhancer function, and maintenance of three-dimensional chromatin structure. Transcriptome analyses in all three patients with point mutations revealed deregulation of genes involved in signal transduction and emphasized the role of CTCF in enhancer-driven expression of genes. Our findings indicate that haploinsufficiency of CTCF affects genomic interaction of enhancers and their regulated gene promoters that drive developmental processes and cognition. Comparison of lymphocyte gene expression between 3 de novo CTCF mutation patients and 8 controls (4 technical replicates each, no biological replicates).
2013-06-01 | E-GEOD-46831 | biostudies-arrayexpress