Format

Send to

Choose Destination
Invest Ophthalmol Vis Sci. 2014 Dec 4;56(1):150-5. doi: 10.1167/iovs.14-15382.

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

Author information

1
Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas, United States Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, United States.
2
Department of Ophthalmology, Peking Union Medical College Hospital, Peking Union Medical College, Beijing, China.
3
Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas, United States Structural and Computational Biology and Molecular Biophysics Graduate Program, Houston, Texas, United States.
4
Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas, United States Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, United States Structural and Computational Biology and Molecular Biophysics Graduate Program, Houston, Texas, United States.

Abstract

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.

KEYWORDS:

NEUROD1; genotype–phenotype correlation; next-generation sequencing; retina; retinitis pigmentosa

PMID:
25477324
PMCID:
PMC4290556
DOI:
10.1167/iovs.14-15382
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Silverchair Information Systems Icon for PubMed Central
Loading ...
Support Center