title: Arg120stop nonsense mutation in the RP2 gene: mutational hotspot and germ line mosaicism?
abstract: Mutations in the RP2 gene account for up to 20% of X-linked recessive retinitis pigmentosa (RP). Arg120stop is to date the most frequently reported mutation found in RP2. Mutation screening was performed during the course of a large screening program of retinal degenerative disorders (RDDs) in South Africa using exon 1 and 2 of RP2 in 20 unrelated families with an X-linked mode of retinal degenerative inheritance. Direct sequencing analysis revealed a C-->T transition at position 358 in the proband in a family of German origin. Subsequent analysis revealed that this Arg120stop mutation cosegregated with the disease in an additional affected family member. The nonsense mutation, Arg120stop, could not however, be detected in the somatic cells of the obligate carrier female. This, the first report of a germ line mutation for a family with RP, has many implications for genetic counseling of retinal degeneration (RD). To avoid inaccurate risk assessment for RP due to epigenetic events, such as the rare occurrence of germ line mosaicism, genetic counseling in families with XLRP should always be guided by molecular testing.
authors.affiliation: Division of Human Genetics, University of Cape Town, Medical School, Observatory, South Africa.
authors.forename: A A
authors.initials: AA
authors.lastname: Vorster
authors.forename: M T
authors.initials: MT
authors.lastname: Rebello
authors.forename: N
authors.initials: N
authors.lastname: Coutts
authors.forename: L
authors.initials: L
authors.lastname: Ehrenreich
authors.forename: A D
authors.initials: AD
authors.lastname: Gama
authors.forename: L J
authors.initials: LJ
authors.lastname: Roberts
authors.forename: R
authors.initials: R
authors.lastname: Goliath
authors.forename: R
authors.initials: R
authors.lastname: Ramesar
authors.forename: L J
authors.initials: LJ
authors.lastname: Greenberg
mesh_terms: D000328:Adult; D000368:Aged; D001120:Arginine / Q000235:genetics; D018389:Codon, Nonsense / Q000235:genetics*; D004252:DNA Mutational Analysis; D044127:Epigenesis, Genetic; D005091:Exons; D005136:Eye Proteins / Q000235:genetics*; D005260:Female; D019204:GTP-Binding Proteins; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D008565:Membrane Proteins; D008870:Microtubules; D009030:Mosaicism / Q000235:genetics*; D010375:Pedigree; D012174:Retinitis Pigmentosa / Q000235:genetics*; D018570:Risk Assessment
chemical_list: D018389:Codon, Nonsense; D005136:Eye Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; C072178:RP2 protein, human; D001120:Arginine; D019204:GTP-Binding Proteins