title: Identification of a novel LCA5 mutation in a Pakistani family with Leber congenital amaurosis and cataracts.
abstract: OBJECTIVE
  To determine the cause of Leber congenital amaurosis (LCA) and developmental cataracts in a consanguineous Pakistani family.
  
  
  METHODS
  The diagnosis was established in all affected individuals of a Pakistani LCA family by medical history, funduscopy, and standard ERG. We performed genome-wide linkage analysis for mapping the disease locus in this family.
  
  
  RESULTS
  Congenitally severely reduced visual acuity and nystagmus were reported for all patients who, in the later phase of the disease, also developed cataracts. LCA in the family cosegregated with homozygosity for a single nucleotide polymorphism (SNP) haplotype on chromosome 6p14.1. The respective candidate region contained Leber congenital amaurosis 5 (LCA5), a gene previously reported to underlie LCA. We subsequently identified a novel truncating mutation in exon 4 of LCA5, c.642delC, in homozygous state in all affected persons of the family.
  
  
  CONCLUSIONS
  We report a novel LCA5 mutation causing LCA in a Pakistani family. Developmental cataracts were present in two of the four patients, raising the possibility that LCA5 mutations may predispose to this additional ocular pathology.
authors.affiliation: Department of Biotechnology and Informatics, BUITEMS, Quetta, Pakistan.
authors.forename: Adeel
authors.initials: A
authors.lastname: Ahmad
authors.forename: Shakeela
authors.initials: S
authors.lastname: Daud
authors.forename: Naseebullah
authors.initials: N
authors.lastname: Kakar
authors.forename: Gudrun
authors.initials: G
authors.lastname: Nürnberg
authors.forename: Peter
authors.initials: P
authors.lastname: Nürnberg
authors.forename: Masroor Ellahi
authors.initials: ME
authors.lastname: Babar
authors.forename: Michaela
authors.initials: M
authors.lastname: Thoenes
authors.forename: Christian
authors.initials: C
authors.lastname: Kubisch
authors.forename: Jamil
authors.initials: J
authors.lastname: Ahmad
authors.forename: Hanno Jörn
authors.initials: HJ
authors.lastname: Bolz
mesh_terms: D000293:Adolescent; D044466:Asian People / Q000235:genetics; D001483:Base Sequence; D002386:Cataract / Q000150:complications / Q000235:genetics* / Q000503:physiopathology; D002648:Child; D003241:Consanguinity; D004252:DNA Mutational Analysis; D005091:Exons; D005123:Eye / Q000378:metabolism* / Q000503:physiopathology; D005136:Eye Proteins / Q000235:genetics; D005260:Female; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes; D006720:Homozygote; D006801:Humans; D057130:Leber Congenital Amaurosis / Q000150:complications / Q000235:genetics* / Q000503:physiopathology; D008297:Male; D008869:Microtubule-Associated Proteins / Q000235:genetics; D008969:Molecular Sequence Data; D009154:Mutation; D020417:Nystagmus, Congenital / Q000150:complications / Q000235:genetics* / Q000503:physiopathology; D010154:Pakistan; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide
chemical_list: D005136:Eye Proteins; C522405:LCA5 protein, human; D008869:Microtubule-Associated Proteins