Baum L, Chan W M, Yeung K Y, Lam D S, Kwok A K, Pang C P
Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong.
Hum Mutat. 2001 May;17(5):436. doi: 10.1002/humu.1127.
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.
RP1基因中的杂合截短突变约占常染色体显性遗传性视网膜色素变性（RP）病例的7%。为研究RP1突变在RP中的作用，我们对101名无亲缘关系的中国RP患者（未按遗传方式选择）和190名老年正常对照者进行筛查，检测编码含2156个氨基酸的RP1蛋白的外显子序列变化。1例患者有突变，因此在中国所有RP病例中，RP1突变导致的病例约占0.0%至5.4%（95%置信区间）。该突变是R677X，这是在美国人中发现的最常见突变。还发现了其他5种已知的序列变化。此外，还鉴定出9种新的序列改变：746G>A（R249H）、1437G>T（M479I）、2116G>C（G706R）、3024G>A（Q1008Q）、3188G>A（Q1063R）、5797C>T（R1933X）、6423A>G（I2141M），以及3'非翻译区的6542C>T和6676T>A变异。1名对照者和1个非RP家族的3名成员为R1933X杂合子，因此该变异可能是一种非致病变异。先前报道的最末端截短是由于Tyr1053（1-bp缺失），发生在RP患者中。因此，在氨基酸1052和1933之间至少存在正常水平的部分RP1似乎是预防RP所必需的。《人类突变》17:436，2001年。
