Screening for mutations in a novel retinal-specific gene among Chinese patients with retinitis pigmentosa.
OBJECTIVE
To identify and evaluate mutations in the RP1 gene among Chinese patients with retinitis pigmentosa (RP).


METHODS
Leukocyte DNA of 92 RP patients were collected in Hong Kong. Sequence changes of the entire coding region of the RP1 gene were examined using PCR, conformation sensitive gel electrophoresis and DNA sequencing.


RESULTS
In total, 1 nonsense mutation and 1 nonsense variant as well as 10 missense alterations were identified in the RP1 gene, among which, Arg677Ter was found in 1 RP patient and another nonsense variant, Arg1933Ter, was identified in 3 normal individuals and 1 patient with Stargardt's disease, suggesting its nonpathogenicity. Arg77Ter is expected to lead to large disruptions of the encoded protein.


CONCLUSIONS
The nonpathogenicity of Arg1933Ter indicates that the C-terminal 224 residues of RP1 protein may be not critical for RP1. The most C-terminal truncation previously reported was due to Tyr1053 (1-bp del) and occurred in RP patients. Thus RP can be caused by reduction in the level of the region of RP1 protein after codon 1052 but before 1933. To ascertain such a proposition, genotypes of more RP patients may reveal more RP causative mutations and more sequence alterations different than those of other ethnic groups.
Xiaoli
Zhang
Z
Center for Molecular Diagnosis and Gene Therapy, Affiliated South-west Hospital, Third Military Medical University, Chongqing 400038.
Weiling
Fu
F
Pang
Chi-Pui
CP
Yeung
Kwun-Yan
KY
D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D018389:Codon, Nonsense; D004252:DNA Mutational Analysis; D005136:Eye Proteins / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D008869:Microtubule-Associated Proteins; D008875:Middle Aged; D020125:Mutation, Missense; D012174:Retinitis Pigmentosa / Q000235:genetics*
D018389:Codon, Nonsense; D005136:Eye Proteins; D008869:Microtubule-Associated Proteins; C120042:RP1 protein, human