title: A novel homozygous Ile535Asn mutation in the rod cGMP phosphodiesterase beta-subunit gene in two brothers of a Japanese family with autosomal recessive retinitis pigmentosa.
abstract: OBJECTIVE
  Recently, mutations in several genes have been identified as being responsible for the pathogenesis of autosomal recessive retinitis pigmentosa (arRP). These genes include rhodopsin, beta-subunit of rod cGMP phosphodiesterase (PDEB), alpha-subunit of rod cGMP phosphodiesterase (PDEA), and alpha-subunit of rod cGMP-gated channel. We here attempted to identify a novel mutation in the PDEB gene in Japanese arRP patients.
  
  
  METHODS
  Using the PCR-SSCP method, sequencing analysis, and restriction endonuclease digestion assay, we analyzed the PDEB gene in 17 Japanese families with non-dominant retinitis pigmentosa.
  
  
  RESULTS
  A novel Ile535Asn mutation was identified in two patients in a single family and the mutation cosegregated with RP in this family. Among 90 unrelated healthy individuals, no one was identified as homozygous for this mutation, except for one individual who was found to be heterozygous.
  
  
  CONCLUSIONS
  Isoleucine at codon 535 in the PDEB gene is conserved among various mammals. Missense mutations of the PDEB gene causing arRP have been reported in a limited region (codon 527-codon 699) in which codon 535 is located. Thus, the Ile535Asn mutation is an additional missense mutation which is responsible for the pathogenesis of arRP.
authors.affiliation: Department of Ophthalmology, Keio University School of Medicine, Tokyo, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Saga
authors.forename: Y
authors.initials: Y
authors.lastname: Mashima
authors.forename: K
authors.initials: K
authors.lastname: Akeo
authors.forename: J
authors.initials: J
authors.lastname: Kudoh
authors.forename: Y
authors.initials: Y
authors.lastname: Oguchi
authors.forename: N
authors.initials: N
authors.lastname: Shimizu
mesh_terms: D015106:3',5'-Cyclic-GMP Phosphodiesterases / Q000235:genetics*; D000328:Adult; D001216:Asparagine / Q000235:genetics; D003062:Codon; D054707:Cyclic Nucleotide Phosphodiesterases, Type 6; D005654:Fundus Oculi; D006801:Humans; D007532:Isoleucine / Q000235:genetics; D007564:Japan; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D010727:Phosphoric Diester Hydrolases; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D017948:Retinal Rod Photoreceptor Cells / Q000201:enzymology*; D012174:Retinitis Pigmentosa / Q000201:enzymology / Q000235:genetics*; D014794:Visual Fields
chemical_list: D003062:Codon; D007532:Isoleucine; D001216:Asparagine; D010727:Phosphoric Diester Hydrolases; D015106:3',5'-Cyclic-GMP Phosphodiesterases; D054707:Cyclic Nucleotide Phosphodiesterases, Type 6; C517431:PDE6B protein, human