Whole exome sequencing revealed 14 variants in NDP, FZD4, LRP5, and TSPAN12 genes for 20 families with familial exudative vitreoretinopathy

• Published in: BMC medical genomics Vol. 15; no. 1; p. 54
• Main Authors: Dan, Handong, Wang, Dongdong, Huang, Zixu, Shi, Qianqian, Zheng, Miao, Xiao, Yuanyuan, Song, Zongming
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 11.03.2022; BioMed Central; BMC
• Subjects: DNA Mutational Analysis; DNA sequencing; Eye Proteins - genetics; Familial Exudative Vitreoretinopathies; Familial exudative vitreoretinopathy; Frizzled Receptors - genetics; FZD4; Genetic aspects; Genetic disorders; Health aspects; Humans; Low Density Lipoprotein Receptor-Related Protein-5 - genetics; LRP5; Mutation; NDP; Nerve Tissue Proteins - genetics; Nucleotide sequencing; Patient outcomes; Pedigree; Proteins; Retinal Diseases - epidemiology; Retinal Diseases - genetics; Tetraspanins - genetics; TSPAN12; Whole Exome Sequencing; China; Familial exudative vitreoretinopathy; LRP5; NDP; TSPAN12; FZD4; Whole exome sequencing
• ISSN: 1755-8794; 1755-8794
• DOI: 10.1186/s12920-022-01204-0

Familial exudative vitreoretinopathy (FEVR) is a complex form of blindness-causing retinal degeneration. This study investigated the potential disease-causing variants in 20 Chinese families with FEVR. All available family members underwent detailed ophthalmological examinations, including best-corrected visual acuity and fundus examination. All probands and most family members underwent fluorescein fundus angiography. Twenty probands underwent whole exome sequencing; 16 of them also underwent copy number variant and mitochondrial genome analysis. Bioinformatics analysis and Sanger sequencing of available family members were used to confirm the disease-causing gene variant. Twenty families were diagnosed with FEVR based on clinical symptoms, fundus manifestations, and fundus fluorescein angiography. Whole exome sequencing revealed 14 variants in NDP, FZD4, LRP5, and TSPAN12 genes among the 13 families. These variants were predicted to be damaging or deleterious according to multiple lines of prediction algorithms; they were not frequently found in multiple population databases. Seven variants had not previously been reported to cause FEVR: c.1039T>G p.(Phe347Val) in the FZD4 gene; c.1612C>T p.(Arg538Trp) and c.3237-2A>C in the LRP5 gene; and c.77T>A p.(Ile26Asn), c.170dupT p.(Leu57Phe fsTer60), c.236T>G p.(Met79Arg) and c.550dupA p.(Arg184Lys fsTer16) in the TSPAN12 gene. We did not detect any variants in the remaining seven families. These results expand the spectrum of variants in the NDP, FZD4, LRP5, and TSPAN12 genes and provide insights regarding accurate diagnosis, family genetic counseling, and future gene therapy for FEVR.