Dataset Information

PRPF3-Associated Autosomal Dominant Retinitis Pigmentosa and CYP4V2-Associated Bietti's Crystalline Corneoretinal Dystrophy Coexist in a Multigenerational Chinese Family.

ABSTRACT: PURPOSE:To characterize the clinical and molecular genetic characteristics of a large, multigenerational Chinese family showing different phenotypes. METHODS:A pedigree consisted of 56 individuals in 5 generations was recruited. Comprehensive ophthalmic examinations were performed in 16 family members affected. Mutation screening of CYP4V2 was performed by Sanger sequencing. Next-generation sequencing (NGS) was performed to capture and sequence all exons of 47 known retinal dystrophy-associated genes in two affected family members who had no mutations in CYP4V2. The detected variants in NGS were validated by Sanger sequencing in the family members. RESULTS:Two compound heterozygous CYP4V2 mutations (c.802-8_810del17insGC and c.992A>C) were detected in the proband who presented typical clinical features of BCD. One missense mutation (c.1482C>T, p.T494M) in the PRPF3 gene was detected in 9 out of 22 affected family members who manifested classical clinical features of RP. CONCLUSIONS:Our results showed that two compound heterozygous CYP4V2 mutations caused BCD, and one missense mutation in PRPF3 was responsible for adRP in this large family. This study suggests that accurate phenotypic diagnosis, molecular diagnosis, and genetic counseling are necessary for patients with hereditary retinal degeneration in some large mutigenerational family.

SUBMITTER: Meng X

PROVIDER: S-EPMC5564071 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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<i>PRPF3</i>-Associated Autosomal Dominant Retinitis Pigmentosa and <i>CYP4V2</i>-Associated Bietti's Crystalline Corneoretinal Dystrophy Coexist in a Multigenerational Chinese Family.

Meng Xiaohong X Li Qiyou Q Guo Hong H Xu Haiwei H Li Shiying S Yin Zhengqin Z

Journal of ophthalmology 20170807

<h4>Purpose</h4>To characterize the clinical and molecular genetic characteristics of a large, multigenerational Chinese family showing different phenotypes.<h4>Methods</h4>A pedigree consisted of 56 individuals in 5 generations was recruited. Comprehensive ophthalmic examinations were performed in 16 family members affected. Mutation screening of <i>CYP4V2</i> was performed by Sanger sequencing. Next-generation sequencing (NGS) was performed to capture and sequence all exons of 47 known retinal ...[more]

PMID: 28848678

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Project description:PurposeTo characterize the spectrum of CYP4V2 gene mutations in 92 unrelated Chinese probands with Bietti's crystalline dystrophy (BCD) and to describe the molecular and clinical characteristics of four novel CYP4V2 mutations associated with BCD.MethodsAll study participants underwent a complete ophthalmological examination. Mutational screening of CYP4V2 coding regions and flanking intron sequences was examined via directional Sanger sequencing, with allele separation confirmed by screening other family members. Subsequent in silico analysis of the mutational consequence on protein function was undertaken, with the impact of the novel mutation on pre-mRNA splicing examined via RT-PCR.ResultsFifteen disease-causing variants were identified in 92 probands with BCD, including four novel mutations and eleven previously reported mutations. The most prevalent mutation was c.802_810del17insGC, which was detected in 69 unrelated families, with an allele frequency of 52.7% (97/184). Homozygosity was revealed in 35 unrelated families, and compound heterozygosity was observed in 43 subjects. Four patients harbored four novel variants, with these mutations cosegregated within all affected individuals and were not found in unaffected family members and 100 unrelated controls. Transcriptional analysis of a novel splice mutation revealed altered RNA splicing. In silico analysis predicted that the missense variant, p.Tyr343Asp, disrupted the CYP4V2 surface electrostatic potential distribution and spatial conformation. Among the patients with four novel mutations, genotype did not always correlate with age at onset, disease course, or electroretinogram (ERG) changes, with phenotypic variations even noted within the same genotype.ConclusionsThe c.802_810del17insCG mutation was the most common mutation in the 92 Chinese probands with BCD examined. Four novel mutations were identified, contributing to the spectrum of CYP4V2 mutations associated with BCD, with no clear link established between disease phenotype and genotype.

Dataset Information

PRPF3-Associated Autosomal Dominant Retinitis Pigmentosa and CYP4V2-Associated Bietti's Crystalline Corneoretinal Dystrophy Coexist in a Multigenerational Chinese Family.

Publications

<i>PRPF3</i>-Associated Autosomal Dominant Retinitis Pigmentosa and <i>CYP4V2</i>-Associated Bietti's Crystalline Corneoretinal Dystrophy Coexist in a Multigenerational Chinese Family.

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