|Title||A homozygous missense mutation in NEUROD1 is associated with nonsyndromic autosomal recessive retinitis pigmentosa.|
|Publication Type||Journal Article|
|Year of Publication||2014|
|Authors||Wang, F, Li, H, Xu, M, Li, H, Zhao, L, Yang, L, Zaneveld, JE, Wang, K, Li, Y, Sui, R, Chen, R|
|Journal||Invest Ophthalmol Vis Sci|
|Date Published||2014 Dec 04|
|Keywords||Adult, 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 Journal||Invest. Ophthalmol. Vis. Sci.|
|PubMed Central ID||PMC4290556|
|Grant List||BR-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