A homozygous missense mutation in NEUROD1 is associated with nonsyndromic autosomal recessive retinitis pigmentosa

Mutations in the same gene can lead to different clinical phenotypes. In this study, we aim to identify novel genotype-phenotype correlations and novel disease genes by analyzing an unsolved autosomal recessive retinitis pigmentosa (ARRP) Han Chinese family. Whole exome sequencing was performed for...

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Bibliographic Details
Published in:Investigative ophthalmology & visual science 2015-01, Vol.56 (1), p.150-155
Main Authors: Wang, Feng, Li, Huajin, Xu, Mingchu, Li, Hui, Zhao, Li, Yang, Lizhu, Zaneveld, Jacques E, Wang, Keqing, Li, Yumei, Sui, Ruifang, Chen, Rui
Format: Article
Language:English
Subjects:
Adult
Basic Helix-Loop-Helix Transcription Factors - genetics
Basic Helix-Loop-Helix Transcription Factors - metabolism
DNA - genetics
DNA Mutational Analysis
Female
Genes, Recessive
Homozygote
Humans
Male
Mutation, Missense
Pedigree
Phenotype
Retinitis Pigmentosa - genetics
Retinitis Pigmentosa - metabolism
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Summary:Mutations in the same gene can lead to different clinical phenotypes. In this study, we aim to identify novel genotype-phenotype correlations and novel disease genes by analyzing an unsolved autosomal recessive retinitis pigmentosa (ARRP) Han Chinese family. Whole exome sequencing was performed for one proband from the consanguineous ARRP family. Stringent variants filtering and prioritizations were applied to identify the causative mutation. A homozygous missense variant, c.724G>A; p.V242I, in NEUROD1 was identified as the most likely cause of disease. This allele perfectly segregates in the family and affects an amino acid, which is highly conserved among mammals. A previous study showed that a homozygous null allele in NEUROD1 causes severe syndromic disease with neonatal diabetes, systematic neurological abnormalities, and early-onset retinal dystrophy. Consistent with these results, our patients who are homozygous for a less severe missense allele presented only late-onset retinal degeneration without any syndromic symptoms. We identified a potential novel genotype-phenotype correlation between NEUROD1 and nonsyndromic ARRP. Our study supports the idea that NEUROD1 is important for maintenance of the retina function and partial loss-of-function mutation in NEUROD1 is likely a rare cause of nonsyndromic ARRP.
ISSN:0146-0404
1552-5783
DOI:10.1167/iovs.14-15382