title: Association of pathogenic mutations in TULP1 with retinitis pigmentosa in consanguineous Pakistani families.
abstract: OBJECTIVE
  To identify pathogenic mutations responsible for autosomal recessive retinitis pigmentosa in 5 consanguineous Pakistani families.
  
  
  METHODS
  Affected individuals in the families underwent a detailed ophthalmological examination that consisted of fundus photography and electroretinography. Blood samples were collected from all participating family members, and genomic DNA was extracted. A genome-wide linkage scan was performed, followed by exclusion analyses among our cohort of nuclear consanguineous families with microsatellite markers spanning the TULP1 locus on chromosome 6p. Two-point logarithm of odds scores were calculated, and all coding exons of TULP1 were sequenced bidirectionally.
  
  
  RESULTS
  The results of ophthalmological examinations among affected individuals in these 5 families were suggestive of retinitis pigmentosa. The genome-wide linkage scan localized the disease interval to chromosome 6p, harboring TULP1 in 1 of 5 families, and sequential analyses identified a single base pair substitution in TULP1 that results in threonine to alanine substitution (p.T380A). Subsequently, we investigated our entire cohort of families with autosomal recessive retinitis pigmentosa and identified 4 additional families with linkage to chromosome 6p, all of them harboring a single base pair substitution in TULP1 that results in lysine to arginine substitution (p.K489R). Results of single-nucleotide polymorphism haplotype analyses were suggestive of a common founder in these 4 families.
  
  
  CONCLUSIONS
  Pathogenic mutations in TULP1 are responsible for the autosomal recessive retinitis pigmentosa phenotype in these consanguineous Pakistani families, with a single ancestral mutation in TULP1 causing the disease phenotype in 4 of 5 families.
  
  
  CONCLUSIONS
  Clinical and molecular characterization of pathogenic mutations in TULP1 will increase our understanding of retinitis pigmentosa at a molecular level.
authors: National Center of Excellence in Molecular Biology, University of the Punjab, Lahore, Pakistan.
authors: Muhammad
authors: M
authors: Iqbal
authors: Muhammad Asif
authors: MA
authors: Naeem
authors: S Amer
authors: SA
authors: Riazuddin
authors: Shahbaz
authors: S
authors: Ali
authors: Tahir
authors: T
authors: Farooq
authors: Zaheeruddin A
authors: ZA
authors: Qazi
authors: Shaheen N
authors: SN
authors: Khan
authors: Tayyab
authors: T
authors: Husnain
authors: Saima
authors: S
authors: Riazuddin
authors: Paul A
authors: PA
authors: Sieving
authors: J Fielding
authors: JF
authors: Hejtmancik
authors: Sheikh
authors: S
authors: Riazuddin
mesh_terms: D002896:Chromosomes, Human, Pair 6 / Q000235:genetics*; D003241:Consanguinity; D004252:DNA Mutational Analysis; D004596:Electroretinography; D005136:Eye Proteins / Q000235:genetics*; D005260:Female; D008040:Genetic Linkage; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D008126:Lod Score; D008297:Male; D018895:Microsatellite Repeats; D009154:Mutation; D010154:Pakistan; D010375:Pedigree; D010781:Photography; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D012174:Retinitis Pigmentosa / Q000175:diagnosis / Q000235:genetics*
chemical_list: D005136:Eye Proteins; C105443:TULP1 protein, human