title: Identification of a novel homozygous nonsense mutation in EYS in a Chinese family with autosomal recessive retinitis pigmentosa.
abstract: BACKGROUND
  Retinitis pigmentosa is the most important hereditary retinal degenerative disease, which has a high degree of clinical and genetic heterogeneity. More than half of all cases of retinitis pigmentosa are autosomal recessive (arRP), but the gene(s) causing arRP in most families has yet to be identified. The purpose of this study is to identify the genetic basis of severe arRP in a consanguineous Chinese family.
  
  
  METHODS
  Linkage and haplotype analyses were used to define the chromosomal location of the pathogenic gene in the Chinese arRP family. Direct DNA sequence analysis of the entire coding region and exon-intron boundaries of EYS was used to determine the disease-causing mutation, and to demonstrate that the mutation co-segregates with the disease in the family.
  
  
  RESULTS
  A single nucleotide substitution of G to T at nucleotide 5506 of EYS was identified in the Chinese arRP family. This change caused a substitution of a glutamic acid residue at codon 1,836 by a stop codon TAA (p.E1836X), and resulted in a premature truncated EYS protein with 1,835 amino acids. Three affected siblings in the family were homozygous for the p.E1836X mutation, while the other unaffected family members carried one mutant allele and one normal EYS allele. The nonsense mutation p.E1836X was not detected in 200 unrelated normal controls.
  
  
  CONCLUSIONS
  The EYS gene is a recently identified disease-causing gene for retinitis pigmentosa, and encodes the orthologue of Drosophila spacemaker. To date, there are only eight mutations in EYS that have been identified to cause arRP. Here we report one novel homozygous nonsense mutation of EYS in a consanguineous Chinese arRP family. Our study represents the first independent confirmation that mutations in EYS cause arRP. Additionally, this is the first EYS mutation identified in the Chinese population.
authors.affiliation: Key Laboratory of Molecular Biophysics of Ministry of Education, College of Life Science and Technology, Center for Human Genome Research, Huazhong University of Science and Technology, Wuhan, Hubei, PR China.
authors.forename: Yukan
authors.initials: Y
authors.lastname: Huang
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
authors.forename: Chang
authors.initials: C
authors.lastname: Li
authors.forename: Guohua
authors.initials: G
authors.lastname: Yang
authors.forename: Mugen
authors.initials: M
authors.lastname: Liu
authors.forename: Qing K
authors.initials: QK
authors.lastname: Wang
authors.forename: Zhaohui
authors.initials: Z
authors.lastname: Tang
mesh_terms: D000595:Amino Acid Sequence; D044466:Asian People / Q000235:genetics; D001483:Base Sequence; D002681:China; D018389:Codon, Nonsense; D003241:Consanguinity; D004252:DNA Mutational Analysis; D004596:Electroretinography; D005091:Exons; D005136:Eye Proteins / Q000737:chemistry / Q000235:genetics*; D005260:Female; D005808:Genes, Recessive; D006239:Haplotypes; D006720:Homozygote; D006801:Humans; D008297:Male; D010375:Pedigree; D012174:Retinitis Pigmentosa / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology
chemical_list: D018389:Codon, Nonsense; C533105:EYS protein, human; D005136:Eye Proteins