Mutations in LRP5,FZD4, TSPAN12, NDP, ZNF408, or KIF11 Genes Account for 38.7% of Chinese Patients With Familial Exudative Vitreoretinopathy

Familial exudative vitreoretinopathy (FEVR) is a severe hereditary retinal disorder characterized by defects in retinal vascular development. To date, six genes have been reported to be responsible for this disease, including LRP5, FZD4, TSPAN12, NDP, ZNF408, and KIF11. The purpose of our study was...

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Published in:	Investigative ophthalmology & visual science 2017-05, Vol.58 (5), p.2623-2629
Main Authors:	Rao, Feng-Qin, Cai, Xue-Bi, Cheng, Fei-Fei, Cheng, Wan, Fang, Xiao-Long, Li, Na, Huang, Xiu-Feng, Li, Li-Hong, Jin, Zi-Bing
Format:	Article
Language:	eng
Subjects:	China - epidemiology DNA Mutational Analysis DNA-Binding Proteins - genetics DNA-Binding Proteins - metabolism Exons Eye Proteins - genetics Eye Proteins - metabolism Female Frizzled Receptors - genetics Frizzled Receptors - metabolism Humans Incidence Kinesin - genetics Kinesin - metabolism Low Density Lipoprotein Receptor-Related Protein-5 - genetics Low Density Lipoprotein Receptor-Related Protein-5 - metabolism Male Mutation Nerve Tissue Proteins - genetics Nerve Tissue Proteins - metabolism Pedigree Phenotype Retinal Diseases - epidemiology Retinal Diseases - genetics Retinal Diseases - metabolism Tetraspanins - genetics Tetraspanins - metabolism Transcription Factors - genetics Transcription Factors - metabolism
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Summary:	Familial exudative vitreoretinopathy (FEVR) is a severe hereditary retinal disorder characterized by defects in retinal vascular development. To date, six genes have been reported to be responsible for this disease, including LRP5, FZD4, TSPAN12, NDP, ZNF408, and KIF11. The purpose of our study was to investigate the genetic defects in Chinese patients with FEVR through mutational analyses of 31 pedigrees. Clinical data and peripheral blood were collected from 31 pedigrees with FEVR. All coding sequences and intron/exon junctions were amplified and sequenced comprehensively, followed by cosegregation testing to verify suspected variants in the family members. Finally, we assessed clinical relevance of the identified mutations, according to the standards and guidelines from the American College of Medical Genetics and Genomics. Twelve index cases (12/31, 38.7%) were confirmed to harbor mutations in the known genes, including one previously reported mutation and 11 novel mutations. Among the detected mutations, LRP5 accounted for the largest proportion with a mean mutation rate of 16.1% (5/31, 16.1%), followed by NDP (3/31, 9.7%), FZD4 (2/31, 6.5%), TSPAN12 (1/31, 3.2%), and KIF11 (1/31, 3.2%). All the novel changes were predicted to be pathogenic by a series of bioinformatics analyses. We comprehensively screened six known disease-causing genes in 31 pedigrees with FEVR and achieved a clear picture of the mutation spectrum in Chinese patients with FEVR, which highlights the importance and utility of clinical genetic diagnosis.
ISSN:	1552-5783 1552-5783