title: RP1 in Chinese: Eight novel variants and evidence that truncation of the extreme C-terminal does not cause retinitis pigmentosa.
abstract: Heterozygous truncating mutations in the RP1 gene cause approximately 7% of autosomal dominant retinitis pigmentosa (RP) cases. To examine the role of RP1 mutations in RP, we screened 101 unrelated Chinese RP patients (unselected for mode of inheritance) and 190 elderly normal control subjects for sequence changes in the coding exons for the 2156 amino acid RP1 protein. One patient had a mutation, thus RP1 mutations cause about 0.0% to 5.4% (95% confidence interval) of all RP among Chinese. The mutation was R677X, the most common found in Americans. Five other known sequence changes were found. In addition, nine novel sequence alterations were identified: 746G>A (R249H), 1437G>T (M479I), 2116G>C (G706R), 3024G>A (Q1008Q), 3188G>A (Q1063R), 5797C>T (R1933X), 6423A>G (I2141M), and the variants 6542C>T and 6676T>A, both in the 3' untranslated region. One control subject and three members of a non-RP family were heterozygous for R1933X, which is therefore likely to be a non-disease-causing variant. The most C-terminal truncation previously reported was due to Tyr1053 (1-bp del) and occurred in RP patients. Thus the presence of a normal level of at least part of RP1 between amino acids 1052 and 1933 appears necessary to prevent RP. Hum Mutat 17:436, 2001.
authors.affiliation: Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong.
authors.forename: L
authors.initials: L
authors.lastname: Baum
authors.forename: W M
authors.initials: WM
authors.lastname: Chan
authors.forename: K Y
authors.initials: KY
authors.lastname: Yeung
authors.forename: D S
authors.initials: DS
authors.lastname: Lam
authors.forename: A K
authors.initials: AK
authors.lastname: Kwok
authors.forename: C P
authors.initials: CP
authors.lastname: Pang
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D000293:Adolescent; D000328:Adult; D000368:Aged; D044466:Asian People / Q000235:genetics*; D002648:Child; D018389:Codon, Nonsense / Q000235:genetics*; D004252:DNA Mutational Analysis; D005091:Exons / Q000235:genetics; D005136:Eye Proteins / Q000737:chemistry* / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005787:Gene Frequency; D005820:Genetic Testing; D014644:Genetic Variation / Q000235:genetics*; D005838:Genotype; D006723:Hong Kong; D006801:Humans; D008297:Male; D008869:Microtubule-Associated Proteins; D008875:Middle Aged; D010375:Pedigree; D010641:Phenotype; D022821:RNA Splice Sites / Q000235:genetics; D012174:Retinitis Pigmentosa / Q000235:genetics* / Q000503:physiopathology*; D017384:Sequence Deletion / Q000235:genetics
chemical_list: D020413:3' Untranslated Regions; D018389:Codon, Nonsense; D005136:Eye Proteins; D008869:Microtubule-Associated Proteins; D022821:RNA Splice Sites; C120042:RP1 protein, human