title: A homozygous missense mutation in NEUROD1 is associated with nonsyndromic autosomal recessive retinitis pigmentosa.
abstract: OBJECTIVE
  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.
authors.affiliation: 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.
authors.forename: Feng
authors.initials: F
authors.lastname: Wang
authors.affiliation: Department of Ophthalmology, Peking Union Medical College Hospital, Peking Union Medical College, Beijing, China.
authors.forename: Huajin
authors.initials: H
authors.lastname: Li
authors.affiliation: 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.
authors.forename: Mingchu
authors.initials: M
authors.lastname: Xu
authors.affiliation: Department of Ophthalmology, Peking Union Medical College Hospital, Peking Union Medical College, Beijing, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Li
authors.affiliation: 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.
authors.forename: Li
authors.initials: L
authors.lastname: Zhao
authors.affiliation: Department of Ophthalmology, Peking Union Medical College Hospital, Peking Union Medical College, Beijing, China.
authors.forename: Lizhu
authors.initials: L
authors.lastname: Yang
authors.affiliation: 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.
authors.forename: Jacques E
authors.initials: JE
authors.lastname: Zaneveld
authors.affiliation: 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.
authors.forename: Keqing
authors.initials: K
authors.lastname: Wang
authors.affiliation: 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.
authors.forename: Yumei
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Ophthalmology, Peking Union Medical College Hospital, Peking Union Medical College, Beijing, China.
authors.forename: Ruifang
authors.initials: R
authors.lastname: Sui
authors.affiliation: 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.
authors.forename: Rui
authors.initials: R
authors.lastname: Chen
mesh_terms: D000328:Adult; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics* / Q000378:metabolism; D004247:DNA / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D005808:Genes, Recessive; D006720:Homozygote; D006801:Humans; D008297:Male; D020125:Mutation, Missense; D010375:Pedigree; D010641:Phenotype; D012174:Retinitis Pigmentosa / Q000235:genetics* / Q000378:metabolism
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D004247:DNA; C093970:NEUROD1 protein, human
keywords: NEUROD1; genotype–phenotype correlation; next-generation sequencing; retina; retinitis pigmentosa