title: Missense mutations at homologous positions in the fourth and fifth laminin A G-like domains of eyes shut homolog cause autosomal recessive retinitis pigmentosa.
abstract: OBJECTIVE
  To describe two novel mutations in the eyes shut homolog (EYS) gene in two families with autosomal recessive retinitis pigmentosa (arRP) from Pakistan and Indonesia.
  
  
  METHODS
  Genome-wide linkage and homozygosity mapping were performed using single nucleotide polymorphism microarray analysis in affected members of the two arRP families. Sequence analysis was performed to identify genetic changes in protein coding exons of EYS.
  
  
  RESULTS
  In the Indonesian and Pakistani families, homozygous regions encompassing the EYS gene at 6q12 were identified, with maximum LOD scores of 1.8 and 3.6, respectively. Novel missense variants in the EYS gene (p.D2767Y and p.D3028Y) were found in the Pakistani and Indonesian families, respectively, that co-segregate with the disease phenotype. Interestingly, the missense variants are located at the same homologous position within the fourth and fifth laminin A G-like domains of EYS.
  
  
  CONCLUSIONS
  To date, mostly protein-truncating mutations have been described in EYS, while only few patients have been described with pathogenic compound heterozygous missense mutations. The mutations p.D2767Y and p.D3028Y described in this study affect highly conserved residues at homologous positions in laminin A G-like domains and support the notion that missense mutations in EYS can cause arRP.
authors.affiliation: Department of Biosciences, COMSATS Institute of Information Technology, Islamabad, Pakistan.
authors.forename: Muhammad Imran
authors.initials: MI
authors.lastname: Khan
authors.forename: Rob W J
authors.initials: RW
authors.lastname: Collin
authors.forename: Kentar
authors.initials: K
authors.lastname: Arimadyo
authors.forename: Shazia
authors.initials: S
authors.lastname: Micheal
authors.forename: Maleeha
authors.initials: M
authors.lastname: Azam
authors.forename: Nadeem
authors.initials: N
authors.lastname: Qureshi
authors.forename: Sultana M H
authors.initials: SM
authors.lastname: Faradz
authors.forename: Anneke I
authors.initials: AI
authors.lastname: den Hollander
authors.forename: Raheel
authors.initials: R
authors.lastname: Qamar
authors.forename: Frans P M
authors.initials: FP
authors.lastname: Cremers
mesh_terms: D000328:Adult; D000595:Amino Acid Sequence; D001483:Base Sequence; D020090:Chromosome Segregation / Q000235:genetics; D019295:Computational Biology; D004252:DNA Mutational Analysis; D004596:Electroretinography; D005136:Eye Proteins / Q000737:chemistry* / Q000235:genetics*; D005190:Family; D005260:Female; D005654:Fundus Oculi; D005808:Genes, Recessive / Q000235:genetics*; D008040:Genetic Linkage; D006801:Humans; D034904:Lamin Type A / Q000737:chemistry*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D020125:Mutation, Missense / Q000235:genetics*; D010375:Pedigree; D017434:Protein Structure, Tertiary; D012174:Retinitis Pigmentosa / Q000235:genetics* / Q000503:physiopathology; D017386:Sequence Homology, Amino Acid
chemical_list: C533105:EYS protein, human; D005136:Eye Proteins; D034904:Lamin Type A