title: Mutations in the β-subunit of rod phosphodiesterase identified in consanguineous Pakistani families with autosomal recessive retinitis pigmentosa.
abstract: OBJECTIVE
  This study was designed to identify pathogenic mutations causing autosomal recessive retinitis pigmentosa (RP) in consanguineous Pakistani families.
  
  
  METHODS
  Two consanguineous families affected with autosomal recessive RP were identified from the Punjab Province of Pakistan. All affected individuals underwent a thorough ophthalmologic examination. Blood samples were collected, and genomic DNAs were extracted. Exclusion analysis was completed, and two-point LOD scores were calculated. Bidirectional sequencing of the β subunit of phosphodiesterase 6 (PDE6β) was completed.
  
  
  RESULTS
  During exclusion analyses both families localized to chromosome 4p, harboring PDE6β, a gene previously associated with autosomal recessive RP. Sequencing of PDE6β identified missense mutations: c.1655G>A (p.R552Q) and c.1160C>T (p.P387L) in families PKRP161 and PKRP183, respectively. Bioinformatic analyses suggested that both mutations are deleterious for the native three-dimensional structure of the PDE6β protein.
  
  
  CONCLUSIONS
  These results strongly suggest that mutations in PDE6β are responsible for the disease phenotype in the consanguineous Pakistani families.
authors.affiliation: National Centre of Excellence in Molecular Biology, University of the Punjab, Lahore, Pakistan.
authors.forename: Shahbaz
authors.initials: S
authors.lastname: Ali
authors.forename: S Amer
authors.initials: SA
authors.lastname: Riazuddin
authors.forename: Amber
authors.initials: A
authors.lastname: Shahzadi
authors.forename: Idrees A
authors.initials: IA
authors.lastname: Nasir
authors.forename: Shaheen N
authors.initials: SN
authors.lastname: Khan
authors.forename: Tayyab
authors.initials: T
authors.lastname: Husnain
authors.forename: Javed
authors.initials: J
authors.lastname: Akram
authors.forename: Paul A
authors.initials: PA
authors.lastname: Sieving
authors.forename: J Fielding
authors.initials: JF
authors.lastname: Hejtmancik
authors.forename: Sheikh
authors.initials: S
authors.lastname: Riazuddin
mesh_terms: D000328:Adult; D000483:Alleles; D000818:Animals; D044466:Asian People / Q000235:genetics*; D001483:Base Sequence; D002894:Chromosomes, Human, Pair 4 / Q000737:chemistry / Q000235:genetics; D003241:Consanguinity; D054707:Cyclic Nucleotide Phosphodiesterases, Type 6 / Q000235:genetics*; D005136:Eye Proteins / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D005808:Genes, Recessive; D006239:Haplotypes; D006801:Humans; D008126:Lod Score; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D010154:Pakistan; D010375:Pedigree; D017948:Retinal Rod Photoreceptor Cells / Q000473:pathology*; D012174:Retinitis Pigmentosa / Q000235:genetics* / Q000473:pathology; D017386:Sequence Homology, Amino Acid
chemical_list: D005136:Eye Proteins; D054707:Cyclic Nucleotide Phosphodiesterases, Type 6; C517431:PDE6B protein, human