[Mutation analysis of retinitis pigmentosa 1 gene in Chinese with retinitis pigmentosa].
OBJECTIVE
To investigate the frequency and pattern of RP1 point mutations in Chinese retinitis pigmentosa (RP) patients and to examine their effects on the development of RP.


METHODS
Conformation sensitive gel electrophoresis (CSGE) and direct DNA sequencing were used to determine sequence alterations occurring in the entire coding region of the RP1 gene in 101 Chinese RP patients in Hong Kong.


RESULTS
R677X was detected in one RP patient. A nonpathogenic nonsense mutation, R1933X, was identified in three normal individuals and one patient with Stargardt disease. The frequency of RP1 mutations among all RP patients in this study is 1/101. R677X is expected to lead to large disruptions of the encoded protein. Additionally, 10 more missense alterations in the RP1 gene were identified in the subjects of this study. Apart from M479I whose pathogenicity can not be determined currently, other sequence changes are just polymorphisms of the RP1 gene.


CONCLUSIONS
The nonpathogenicity of R1933X indicates that the C-terminal 224 residues of RP1 protein may be not critical for RP1. Recently, a C-termnal truncating mutation, Y1053(1 bp del), was reported to occur in an RP patient. Thus RP can be caused by lack of the region of RP1 protein after codon 1052 but before 1933. To confirm such a proposition, a large genotyping study is necessary and is likely to reveal more RP causative mutations and uncover more sequence alterations different from those of other ethnic groups.
Zhang
Xiaoli
X
Affiliated Southwest Hospital, Third Military Medical University, Chongqing, 400038 P. R. China. weilingfu@yahoo.com
Yeung
Kwun-Yan
KY
Pang
Chi-Pui
CP
Fu
Weiling
W
D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D002681:China; D004247:DNA / Q000737:chemistry / Q000235:genetics; D004252:DNA Mutational Analysis; D005136:Eye Proteins / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D008297:Male; D008869:Microtubule-Associated Proteins; D008875:Middle Aged; D009154:Mutation; D020125:Mutation, Missense; D012174:Retinitis Pigmentosa / Q000235:genetics*
D005136:Eye Proteins; D008869:Microtubule-Associated Proteins; C120042:RP1 protein, human; D004247:DNA