Identification of a<i>PRX</i>variant in a Chinese family with congenital cataract by exome sequencing

Yuan, Lamei; Yi, Junhui; Lin, Qiongfen; Xu, Hongbo; Deng, Xiong; Wang, Xiong; Xiao, Jingjing; Jiang, Chuanhai; Yuan, Xinrong; Chen, Yong; Deng, Hao

doi:10.1093/qjmed/hcw058

Cited by 13 publications

(6 citation statements)

References 22 publications

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“…Neither of these syndromes include cataract as a presenting clinical feature. However, PRX variants of uncertain significance (p.R129H, p.V1225M) have been associated with congenital cataract in humans [ Yuan et al . 2016 ; Jones et al .…”

Section: Discussionmentioning

confidence: 99%

Whole-exome sequencing prioritizes candidate genes for hereditary cataract in the Emory mouse mutant

Bennett

Zhou

Meyer

et al. 2023

G3: Genes, Genomes, Genetics

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The Emory cataract (Em) mouse mutant has long been proposed as an animal model for age-related or senile cataract in humans – a leading cause of visual impairment. However, the genetic defect(s) underlying the autosomal dominant Em phenotype remains elusive. Here, we confirmed development of the cataract phenotype in commercially available Em/J mice (but not ancestral CFW mice) at 6-8 months-of-age and undertook whole-exome sequencing of candidate genes for Em. Analysis of coding and splice-site variants did not identify any disease causing/associated mutations in over 450 genes known to underlie inherited and age-related forms of cataract and other lens disorders in humans and mice, including genes for lens crystallins, membrane/cytoskeleton proteins, DNA/RNA-binding proteins, and those associated with syndromic/systemic forms of cataract. However, we identified three cataract/lens-associated genes each with one novel homozygous variant including predicted missense substitutions in Prx (p.R167C) and Adamts10 (p.P761L) and a disruptive in-frame deletion variant (predicted missense) in Abhd12 (p.L30_A32delinsS) that were absent in CFW and over 35 other mouse strains. In silico analysis predicted that the missense substitutions in Prx and Adamts10 were borderline neutral/damaging and neutral, respectively, at the protein function level, whereas, that in Abhd12 was functionally damaging. Both the human counterparts of Adamts10 and Abhd12 are clinically associated with syndromic forms of cataract known as Weil-Marchesani syndrome 1 and polyneuropathy, hearing loss, ataxia, retinitis pigmentosa, and cataract (PHARC) syndrome, respectively. Overall, while we cannot exclude Prx and Adamts10, our data suggest that Abhd12 is a promising candidate gene for cataract in the Em/J mouse.

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Section: Discussionmentioning

confidence: 99%

Whole-exome sequencing prioritizes candidate genes for hereditary cataract in the Emory mouse mutant

Bennett

Zhou

Meyer

et al. 2023

G3: Genes, Genomes, Genetics

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“…Peripheral blood was drawn from six family members. Genomic DNA (gDNA) was extracted from blood using a phenol-chloroform extraction strategy as previously described [22,23].…”

Section: Methodsmentioning

confidence: 99%

Identification of novel pathogenic ABCA4 variants in a Han Chinese family with Stargardt disease

Qin

Cao

et al. 2019

Bioscience Reports

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Stargardt disease (STGD1, OMIM 248200) is a common hereditary juvenile or early adult onset macular degeneration. It ultimately leads to progressive central vision loss. Here, we sought to identify gene mutations associated with STGD1 in a three-generation Han Chinese pedigree by whole exome sequencing and Sanger sequencing. Two novel potentially pathogenic variants in a compound heterozygous state, c.3607G>T (p.(Gly1203Trp)) and c.6722T>C (p.(Leu2241Pro)), in the ATP binding cassette subfamily A member 4 gene (ABCA4) were identified as contributing to the family’s STGD1 phenotype. These variants may impact the ABCA4 protein structure and reduce the retinal-activated ATPase activity, leading to abnormal all-trans retinal accumulation in photoreceptor outer segments and in retinal pigment epithelium cells. The present study broadens the mutational spectrum of the ABCA4 responsible for STGD1. A combination of whole exome sequencing and Sanger sequencing is likely to be a time-saving and cost-efficient approach to screen pathogenic variants in genetic disorders caused by sizable genes, as well as avoiding misdiagnosis. These results perhaps refine genetic counseling and ABCA4-targetted treatments for families affected by STGD1.

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“…Genomic DNA (gDNA) was separated from peripheral blood lymphocytes via a phenol–chloroform extraction (Huang et al, ). Proband (IV:1) exome sequencing was performed for unveiling genetic causation of EVC in this pedigree, following the established protocol of BGI‐Shenzhen (Fan et al, ; Yuan et al, ). A paired‐end DNA library was constructed and whole‐exome capture was performed utilizing BGI exome V4 kit.…”

Section: Methodsmentioning

confidence: 99%

Identification of a novel EVC variant in a Han‐Chinese family with Ellis‐van Creveld syndrome

Huang

Guo

et al. 2019

Molec Gen & Gen Med

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Background Ellis‐van Creveld syndrome (EVC), a very rare genetic skeletal dysplasia, is clinically characterized by a tetrad consisting of chondrodystrophy, polydactyly, ectodermal dysplasia, and cardiac anomalies. The aim of this study was to identify the genetic defect for EVC in a five‐generation consanguineous Han‐Chinese pedigree. Methods A five‐generation, 12‐member Han‐Chinese pedigree was enrolled in this study. Exome sequencing was applied in the proband to screen potential genetic variant(s), and then Sanger sequencing was used to identify the variant in family members and 200 unrelated ethnicity‐matched controls. Results A novel homozygous variant, c.2014C>T, p.(Q672*), in the EvC ciliary complex subunit 1 gene (EVC), was detected in the patient, which was cosegregated with the disease in the family and absent in the controls. Conclusion The identified novel homozygous EVC variant, c.2014C>T, p.(Q672*), was responsible for EVC in this Han‐Chinese pedigree. The findings in this study extend the EVC mutation spectrum and may provide new insights into EVC causation and diagnosis with implications for genetic counseling and clinical management.

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Identification of aPRXvariant in a Chinese family with congenital cataract by exome sequencing

Cited by 13 publications

References 22 publications

Whole-exome sequencing prioritizes candidate genes for hereditary cataract in the Emory mouse mutant

Whole-exome sequencing prioritizes candidate genes for hereditary cataract in the Emory mouse mutant

Identification of novel pathogenic ABCA4 variants in a Han Chinese family with Stargardt disease

Identification of a novel EVC variant in a Han‐Chinese family with Ellis‐van Creveld syndrome

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