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Identification of novel CYP4V2 gene mutations in 92 Chinese families with Bietti’s crystalline corneoretinal dystrophy
PURPOSE: To 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. METHODS: All study participants underwent a complet...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Molecular Vision
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4287718/ https://www.ncbi.nlm.nih.gov/pubmed/25593508 |
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author | Meng, Xiao Hong Guo, Hong Xu, Hai Wei Li, Qi You Jin, Xin Bai, Yun Li, Shi Ying Yin, Zheng Qin |
author_facet | Meng, Xiao Hong Guo, Hong Xu, Hai Wei Li, Qi You Jin, Xin Bai, Yun Li, Shi Ying Yin, Zheng Qin |
author_sort | Meng, Xiao Hong |
collection | PubMed |
description | PURPOSE: To 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. METHODS: All 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. RESULTS: Fifteen 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. CONCLUSIONS: The 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. |
format | Online Article Text |
id | pubmed-4287718 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Molecular Vision |
record_format | MEDLINE/PubMed |
spelling | pubmed-42877182015-01-15 Identification of novel CYP4V2 gene mutations in 92 Chinese families with Bietti’s crystalline corneoretinal dystrophy Meng, Xiao Hong Guo, Hong Xu, Hai Wei Li, Qi You Jin, Xin Bai, Yun Li, Shi Ying Yin, Zheng Qin Mol Vis Research Article PURPOSE: To 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. METHODS: All 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. RESULTS: Fifteen 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. CONCLUSIONS: The 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. Molecular Vision 2014-12-31 /pmc/articles/PMC4287718/ /pubmed/25593508 Text en Copyright © 2014 Molecular Vision. http://creativecommons.org/licenses/by-nc-nd/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited, used for non-commercial purposes, and is not altered or transformed. |
spellingShingle | Research Article Meng, Xiao Hong Guo, Hong Xu, Hai Wei Li, Qi You Jin, Xin Bai, Yun Li, Shi Ying Yin, Zheng Qin Identification of novel CYP4V2 gene mutations in 92 Chinese families with Bietti’s crystalline corneoretinal dystrophy |
title | Identification of novel CYP4V2 gene mutations in 92 Chinese families with Bietti’s crystalline corneoretinal dystrophy |
title_full | Identification of novel CYP4V2 gene mutations in 92 Chinese families with Bietti’s crystalline corneoretinal dystrophy |
title_fullStr | Identification of novel CYP4V2 gene mutations in 92 Chinese families with Bietti’s crystalline corneoretinal dystrophy |
title_full_unstemmed | Identification of novel CYP4V2 gene mutations in 92 Chinese families with Bietti’s crystalline corneoretinal dystrophy |
title_short | Identification of novel CYP4V2 gene mutations in 92 Chinese families with Bietti’s crystalline corneoretinal dystrophy |
title_sort | identification of novel cyp4v2 gene mutations in 92 chinese families with bietti’s crystalline corneoretinal dystrophy |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4287718/ https://www.ncbi.nlm.nih.gov/pubmed/25593508 |
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