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

TitleA homozygous missense mutation in NEUROD1 is associated with nonsyndromic autosomal recessive retinitis pigmentosa.
Publication TypeJournal Article
Year of Publication2014
AuthorsWang, F, Li, H, Xu, M, Li, H, Zhao, L, Yang, L, Zaneveld, JE, Wang, K, Li, Y, Sui, R, Chen, R
JournalInvest Ophthalmol Vis Sci
Date Published2014 Dec 04
KeywordsAdult, Basic Helix-Loop-Helix Transcription Factors, DNA, DNA Mutational Analysis, Female, Genes, Recessive, Homozygote, Humans, Male, Mutation, Missense, Pedigree, Phenotype, Retinitis Pigmentosa

PURPOSE: 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.

METHODS: 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.

RESULTS: 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.

CONCLUSIONS: 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.

Alternate JournalInvest. Ophthalmol. Vis. Sci.
PubMed ID25477324
PubMed Central IDPMC4290556
Grant ListBR-GE-0613-0618-BCM / BC / NCI NIH HHS / United States
U54 HD083092 / HD / NICHD NIH HHS / United States
R01EY018571 / EY / NEI NIH HHS / United States
S10 RR026550 / RR / NCRR NIH HHS / United States
R01 EY022356 / EY / NEI NIH HHS / United States
R01 EY018571 / EY / NEI NIH HHS / United States
R01EY022356 / EY / NEI NIH HHS / United States

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