Ocular Features and Mutation Spectrum of Patients With Familial Exudative Vitreoretinopathy

Abstract

Purpose To investigate the clinical findings in Chinese patients diagnosed with familial exudative vitreoretinopathy (FEVR) and carrying pathogenic mutations. Methods One hundred twenty unrelated patients with FEVR were enrolled in this study. Genomic DNA and ophthalmic examinations were collected from all the patients and their available relatives. Targeted next-generation sequencing was performed to detect mutations. In silico programs were used to evaluate the pathogenicity of all the mutations. Results Eighty identified mutations were found in 81 unrelated patients (31/81 in LRP5 , 25/81 in FZD4 , 12/81 in TSPAN12 , 8/81 in NDP , 4/81 in KIF11 , and 1/81 in ZNF408 ). Among those mutations, 53 were novel (23/35 in LRP5 , 15/21 in FZD4 , 8/11 in TSPAN12 , 3/8 in NDP , 3/4 in KIF11 , 1/1 in ZNF408 ). Patients with LRP5, FZD4 , TSPAN12 , or NDP mutations were mainly classified into stage 4 and stage 5 and one-half of patients with KIF11 mutations were in stage 4. In addition, all the patients in NDP group were found to have bilateral symmetry in FEVR stage. Conclusions Our results present profound phenotypic variability and a wide mutation spectrum of FEVR in the Chinese population, which could be useful for a precise and comprehensive genetic diagnosis for patients with FEVR in the future.

Long-Term Clinical Outcomes and Genotype–phenotype Correlation in Familial Exudative Vitreoretinopathy in a Tertiary Referral Center

“…This is in contrast with other studies performed in Chinese populations. 4,9 In the study by Tao et al, 9 LRP5 was the most common mutation in 81 identified mutations. Wang et al 4 found that Chinese patients with mutations in NDP, TSPAN12, or KIF11 were more likely to have bilateral symmetrical severe retinopathy as compared with patients with LRP5 and FZD4 mutations that displayed milder but broader spectrum of phenotypes and higher frequency of asymmetry.…”

“…Recent studies have focused on elucidating the genetic spectrum of FEVR. 3,4,9,10 Few studies have compared the clinical presentations and outcomes of genetic-positive versus genetic-negative patients. We found that genetic-negative patients were more likely to have a history of preterm birth.…”

Congenital X-linked Retinoschisis and Familial Exudative Vitreoretinopathy: Pathogenesis, Diagnosis, and Treatment

“…Bu bulguların FEVR için doğru tanı, genetik danışmalık ve gelecekte mümkün olabilecek gen tedavileri için yararlı olacağını düşünmekteyiz. [44,45] Sonuç KXR klinik ve OKT görüntüleme ile tanı konulabilen ancak günümüzde etkin tedavisi olmayan bir kalıtsal fundus distrofisidir. Stabil seyreden ve makulaya ilerlemeyen periferik skizis bulunan olguların takibi önerilmekle birlikte, retina dekolmanı ve vitreus hemorajisi gibi komplikasyon gelişen olgular vitrektomiden fayda görebilir.…”

Identification of Five Novel Variants in the TSPAN12 Gene in Chinese Families With Familial Exudative Vitreoretinopathy

“…The clinical features of FEVR vary widely, ranging from slight peripheral retinal vascular anomalies with no visual impairment to total blindness caused by severe retinal detachment. 2 – 6 As a genetic disease, FEVR can be inherited in an autosomal dominant, autosomal recessive, or X-linked pattern. Sixteen genes and 1 locus including FZD4, 7 NDP , 8 LRP5 , 9 TSPAN12 , 10 ZNF408 , 11 KIF11 , 12 RCBTB1 , 13 CTNNB1 , 14 ILK , 15 JAG1 , 16 ATOH7 , 17 CTNNA1 , 18 CTNND1 , 19 LRP6 , 20 DGL1 , 21 TGFBR2 , 22 and EVR3 23 had been identified to be associated with FEVR.…”