title: Genetic analysis of Indian families with autosomal recessive retinitis pigmentosa by homozygosity screening.
abstract: OBJECTIVE
  To identify the disease-causing genes in families with autosomal recessive RP (ARRP).
  
  
  METHODS
  Families were screened for homozygosity at candidate gene loci followed by screening of the selected gene for pathogenic mutations if homozygosity was present at a given locus. A total of 34 families were included, of which 24 were consanguineous. Twenty-three genes were selected for screening. The presence of homozygosity was assessed by genotyping flanking microsatellite markers at each locus in affected individuals. Mutations were detected by sequencing of coding regions of genes. Sequence changes were tested for presence in 100 or more unrelated normal control subjects and for cosegregation in family members.
  
  
  RESULTS
  Homozygosity was detected at one or more loci in affected individuals of 10 of 34 families. Homozygous disease cosegregating sequence changes (two frame-shift, two missense, and one nonsense; four novel) were found in the TULP1, RLBP1, ABCA4, RPE65, and RP1 genes in 5 of 10 families. These changes were absent in 100 normal control subjects. In addition, several polymorphisms and novel variants were found. All the putative pathogenic changes were associated with severe forms of RP with onset in childhood. Associated macular degeneration was found in three families with mutations in TULP1, ABCA4, and RP1 genes.
  
  
  CONCLUSIONS
  Novel mutations were found in different ARRP genes. Mutations were detected in approximately 15% (5/34) of ARRP families tested, suggesting involvement of other genes in the remaining families.
authors.affiliation: Kallam Anji Reddy Molecular Genetics Laboratory, Champalimaud Translational Centre for Eye Research, Hyderabad Eye Research Foundation, Hyderabad, India.
authors.forename: Hardeep Pal
authors.initials: HP
authors.lastname: Singh
authors.forename: Subhadra
authors.initials: S
authors.lastname: Jalali
authors.forename: Raja
authors.initials: R
authors.lastname: Narayanan
authors.forename: Chitra
authors.initials: C
authors.lastname: Kannabiran