Novel C8orf37 Mutations in Patients with Early-onset Retinal Dystrophy, Macular Atrophy, Cataracts, and High Myopia

ABSTRACT

Purpose: More than 50 genes are reported as causative genes of autosomal recessive (ar) retinitis pigmentosa (RP) and cone-rod dystrophy (CRD). It is challenging to identify causative mutations for arRP and arCRD. The purpose of the present study was to investigate clinical and genetic features of two siblings with early-onset retinal dystrophy.

Methods: Whole-exome sequencing was conducted for the two affected siblings and their unaffected brother and mother from a Japanese family. We performed complete ophthalmic examinations, including visual acuity, funduscopy, visual-field testing, electroretinography and optical coherence tomography.

Results: Whole-exome sequencing analysis identified novel compound heterozygous mutations, a splice site mutation (c.374 + 2T > C in intron 4) and a deletion mutation (c.575delC [p.T192MfsX28] in exon 6) of chromosome 8 open reading frame 37 (C8orf37) gene, which encodes a ciliary protein, in both patients. The mother carried the truncating mutation, and the brother carried neither mutation. Ophthalmic examinations revealed diffuse retinal degeneration, macular atrophy, non-recordable electroretinography responses, cataracts, and high myopia in both patients, who could not be diagnosed with either RP or CRD because of the severe retinal degeneration and early onset disease. Longitudinal follow-up of the patients revealed highly progressive retinal degeneration, macular atrophy, and visual field loss.

Conclusions: Recessive C8orf37 mutations have been identified in early to adolescent-onset arRP and arCRD with macular involvement. Our study identified two novel truncating mutations of the C8orf37 gene in siblings with early-onset retinal dystrophy, macular atrophy, cataracts, and high myopia.

• C8orf37
• early-onset retinal dystrophy
• mutation
• whole-exome sequencing

Acknowledgments

We thank the patients and their families for participation in this study.

Declaration of interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article.

Funding

This study was supported by grants to T.I. from the Ministry of Health, Labor and Welfare of Japan [13803661], to M.A. and T.H. from the Ministry of Education, Culture, Sports, Science and Technology of Japan [Grant-in-Aid for Scientific Research C, 25462744 and 25462738], and to T.H. from the Vehicle Racing Commemorative Foundation.