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ABSTRACT:
PROVIDER: PRJNA892754 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Syndactyly type 1 (SD1) is an autosomal dominant limb malformation characterized in its classical form by complete or partial webbing between the third and fourth fingers and/or the second and third toes. Four subtypes (a, b, c and d) are defined based on variable phenotypes, but the disease genes remain unidentified. SD1-a have been mapped to chromosome 3p21.31 and SD1-b to 2q34-q36. SD1-c and SD1-d are very rare and no gene loci are known for them. We performed linkage and haplotype analyses in two Han Chinese families with SD1-c, and refined the disease locus to 2q31- 2q32. In the large family A, mutation of c.917G>A (p.R306Q) in the homodomain of HOXD13 was indentified. Family B was confirmed with genetic homogeneity and the mutation was c.916C>G (p.R306G). CNV analysis by array CGH excluded possible microdeletion or microduplication. SD1c patient sample in the SD1c family vs common control outside the family, healthy control sample in the SD1c family vs common control outside the family
2014-06-01 | E-GEOD-55181 | biostudies-arrayexpress
Project description:The paired box gene 6 (PAX6) is an essential transcription factor for eye formation. Genetic alterations in PAX6 can lead to various ocular malformations including aniridia. The purpose of this study was to identify genetic defects as the underlying cause of familial coloboma of iris in a large Chinese family. After linkage analysis was carried out in this family, all exons of PAX6 in the proband were sequenced by the Sanger sequencing technique. Then the genome of the proband was evaluated by a microarray-based comparative genomic hybridization (aCGH). Quantitative real-time PCR was applied to verify the abnormal aCGH findings. All patients presented bilateral partial coloboma of iris, severe congenital nystagmus, hyperpresbyopia and congenital posterior polar cataracts. Two-point linkage analysis in the autosomal dominant family showed loss of heterozygosity at the D11S914 locus. There was no pathogenic mutation in the exons of PAX6. The aCGH analysis revealed a 681 kb heterozygous deletion on chromosome 11p13. Quantitative real-time PCR verified the deletion in the patients and further confirmed this deletion cosegregation with the coloboma of iris phenotype in the family. The 681 kb large deletion of chromosome 11p13 downstream of PAX6 is the genetic cause of the familial coloboma of ocular in this large Chinese family. aCGH should be applied if there is a negative result for the mutation detection of PAX6 in patients with aniridia. One Case sample and one control sample
2013-09-05 | E-GEOD-50577 | biostudies-arrayexpress
Project description:The paired box gene 6 (PAX6) is an essential transcription factor for eye formation. Genetic alterations in PAX6 can lead to various ocular malformations including aniridia. The purpose of this study was to identify genetic defects as the underlying cause of familial coloboma of iris in a large Chinese family. After linkage analysis was carried out in this family, all exons of PAX6 in the proband were sequenced by the Sanger sequencing technique. Then the genome of the proband was evaluated by a microarray-based comparative genomic hybridization (aCGH). Quantitative real-time PCR was applied to verify the abnormal aCGH findings. All patients presented bilateral partial coloboma of iris, severe congenital nystagmus, hyperpresbyopia and congenital posterior polar cataracts. Two-point linkage analysis in the autosomal dominant family showed loss of heterozygosity at the D11S914 locus. There was no pathogenic mutation in the exons of PAX6. The aCGH analysis revealed a 681 kb heterozygous deletion on chromosome 11p13. Quantitative real-time PCR verified the deletion in the patients and further confirmed this deletion cosegregation with the coloboma of iris phenotype in the family. The 681 kb large deletion of chromosome 11p13 downstream of PAX6 is the genetic cause of the familial coloboma of ocular in this large Chinese family. aCGH should be applied if there is a negative result for the mutation detection of PAX6 in patients with aniridia.
2013-09-05 | GSE50577 | GEO
Project description:Syndactyly type 1 (SD1) is an autosomal dominant limb malformation characterized in its classical form by complete or partial webbing between the third and fourth fingers and/or the second and third toes. Four subtypes (a, b, c and d) are defined based on variable phenotypes, but the disease genes remain unidentified. SD1-a have been mapped to chromosome 3p21.31 and SD1-b to 2q34-q36. SD1-c and SD1-d are very rare and no gene loci are known for them. We performed linkage and haplotype analyses in two Han Chinese families with SD1-c, and refined the disease locus to 2q31- 2q32. In the large family A, mutation of c.917G>A (p.R306Q) in the homodomain of HOXD13 was indentified. Family B was confirmed with genetic homogeneity and the mutation was c.916C>G (p.R306G). CNV analysis by array CGH excluded possible microdeletion or microduplication.
2014-06-01 | GSE55181 | GEO
Project description:Wolfram syndrome, an autosomal recessive disorder characterized by juvenile-onset diabetes mellitus and optic atrophy, is caused by mutations in the WFS1 gene. WFS1 encodes an endoplasmic reticulum resident transmembrane protein. The Wfs1-null mice exhibit progressive insulin deficiency and diabetes. The aim of the present study was to describe the insulin secretion and transcriptome of pancreatic islets in WFS1-deficient mice. WFS1-deficient (Wfs1KO) mice had considerably less pancreatic islets than heterozygous (Wfs1HZ) or wild-type (WT) mice. Wfs1KO pancreatic islets secreted less insulin after stimulation with 2 and 10 mM glucose and with tolbutamide solution compared to WT and Wfs1HZ islets, but not after stimulation with 20 mM glucose. Differences in proinsulin amount were not statistically significant although there was a trend that Wfs1KO had an increased level of proinsulin. After stimulation with 2 mM glucose solution the proinsulin/insulin ratio in Wfs1KO was significantly higher than that of WT and Wfs1HZ. RNA-seq from pancreatic islets found melastatin-related transient receptor potential subfamily member 5 protein gene (Trpm5) to be downregulated in WFS1-deficient mice. Functional annotation of RNA sequencing results showed that WFS1 deficiency influenced significantly the pathways related to tissue morphology, endocrine system development and function, molecular transport network. These findings suggest an interactive role of WFS1 and TRPM5 in insulin secretion. 12 samples: three genotypes, 4 individuals in each genotype
2015-02-14 | E-GEOD-65929 | biostudies-arrayexpress
Project description:Wolfram syndrome is a rare genetic disorder largely caused by pathogenic variants in the WFS1 gene and manifested by diabetes mellitus, optic nerve atrophy, and progressive neurodegeneration. Recent genetic and clinical findings have revealed Wolfram syndrome as a spectrum disorder. Therefore, a genotype-phenotype correlation analysis is needed for diagnosis and therapeutic development. Here, we focus on the WFS1 c.1672C>T, p.R558C variant which is highly prevalent in the Ashkenazi-Jewish population. Clinical investigation indicates that subjects carrying the homozygous WFS1 c.1672C>T, p.R558C variant show mild forms of Wolfram syndrome phenotypes. Expression of WFS1 p.R558C is more stable compared to the other known recessive pathogenic variants associated with Wolfram syndrome. Human induced pluripotent stem cell (iPSC)-derived islets (SC-islets) homozygous for WFS1 c.1672C>T variant recapitulate genotype-related Wolfram syndrome phenotypes. Enhancing residual WFS1 function by a combination treatment of chemical chaperones mitigates detrimental effects caused by the WFS1 c.1672C>T, p.R558C variant and increases insulin secretion in SC-islets. Thus, the WFS1 c.1672C>T, p.R558C variant causes a mild form of Wolfram syndrome phenotypes, which can be remitted with a combination treatment of chemical chaperones. We demonstrate that our patient iPSC-derived disease model provides a valuable platform for further genotype-phenotype analysis and therapeutic development for Wolfram syndrome.
2022-09-01 | GSE212256 | GEO
Project description:The autosomal recessive Perrault syndrome with juvenile ovarian failure, progressive sensorineural deafness, ataxia and leukoencephalopathy can be caused by loss of function mutations in CLPP. This gene encodes a peptidase that is conserved since bacteria and localizes to mitochondrial matrix in eukaryotes. Here, assembly and stability of mitochondrial complexes from adult Clpp-/- mouse brains were analyzed by Complexome profiling.
2022-02-17 | PXD025478 | Pride