Dataset Information

Novel mutations in CYP4V2 in Bietti corneoretinal crystalline dystrophy: Next-generation sequencing technology and genotype-phenotype correlations.

ABSTRACT: Purpose:To identify any novel mutations in CYP4V2 in 85 Chinese families with Bietti corneoretinal crystalline dystrophy (BCD) by using next-generation sequencing, and to summarize the mutation spectrum in this population, along with any genotype-phenotype correlations. Methods:A total of 90 patients with BCD from 85 unrelated Chinese families were recruited. All probands were analyzed by using gene chip-based next-generation sequencing, to capture and sequence all the exons of 57 known hereditary retinal degeneration-associated genes. The candidate variants were validated with PCR and Sanger sequencing. Results:Twenty-eight mutations were detected in all patients, including thirteen novel mutations (five missense, six deletions, one splicing and one frame-shift mutations) and 15 previously reported mutations. Mutations in 64 patients were inherited from their parents, while three patients had de novo mutations. c.802-8_810del17insGC was the most common mutation, accounting for 78% of the mutations. Although 16 patients were homozygous at this site, the clinical features of all 16 patients were highly heterogeneous. Conclusions:These results expand the spectrum of mutations in CYP4V2, and suggest that mutations in CYP4V2 may be common in the Chinese population. The phenotype of patients with the homozygous mutation (hom.c.802-8_810del17insGC) is highly heterogeneous.

SUBMITTER: Meng XH

PROVIDER: S-EPMC6828992 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Novel mutations in <i>CYP4V2</i> in Bietti corneoretinal crystalline dystrophy: Next-generation sequencing technology and genotype-phenotype correlations.

Meng Xiao Hong XH He Yan Y Zhao Tong Tao TT Li Shi Ying SY Liu Yong Y Yin Zheng Qin ZQ

Molecular vision 20191031

<h4>Purpose</h4>To identify any novel mutations in <i>CYP4V2</i> in 85 Chinese families with Bietti corneoretinal crystalline dystrophy (BCD) by using next-generation sequencing, and to summarize the mutation spectrum in this population, along with any genotype-phenotype correlations.<h4>Methods</h4>A total of 90 patients with BCD from 85 unrelated Chinese families were recruited. All probands were analyzed by using gene chip-based next-generation sequencing, to capture and sequence all the exon ...[more]

PMID: 31741654

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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

Novel mutations in CYP4V2 in Bietti corneoretinal crystalline dystrophy: Next-generation sequencing technology and genotype-phenotype correlations.

Publications

Novel mutations in <i>CYP4V2</i> in Bietti corneoretinal crystalline dystrophy: Next-generation sequencing technology and genotype-phenotype correlations.

Similar Datasets

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