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目的：比较中国与日本视网膜母细胞瘤(retinoblastoma,RB)患者RB1基因突变发生的位点，了解其RB1基因突变的特点。方法：应用PCR-SSCP/异源双链法筛查新收集RB患者的白细胞基因组DNA，测序分析确定突变。结合以前的工作，分析中国与日本RB患者RB1基因突变发生的特性。结果：在新收集的RB患者中，确定4例RB1基因生殖细胞性突变：G→T(GGA→TGA)/Gly86stop;delTT(ACTTGG→ACGG)/CODON76～77;C→T(CAT→TAT)/His129Tyr;TT→A(ATTCCT→ATACT)/codon369～370。结合以前的报道，我们共确定了21个突变，散发11个外显子及3个内含子。85%突变形成截断蛋白，95%突变影响RB蛋白(pRB)大袋立体结构。点突变所占比例最高(52%)；复杂突变所占比例虽然只有10%，但比国外报道的比例(2%)高出许多。结论：中国与日本RB患者RB1基因突变以微小突变为主，散发在多个不同的外显子，绝大部分严重影响pRB的正常功能。突变方式有所侧重，复杂突变的比例相对较高，存在一定的种族特异性。
OBJECTIVE: To compare the occurrence of RB1 gene mutation in Chinese and Japanese retinoblastoma (RB) patients and to understand the characteristics of RB1 gene mutation. METHODS: PCR-SSCP/heterologous double-stranded screening was used to screen white blood cell genomic DNA from newly-collected RB patients. Sequencing analysis was used to identify mutations. Combined with previous work, the characteristics of RB1 gene mutation in Chinese and Japanese RB patients were analyzed. Results: Among the newly collected RB patients, 4 germline mutations of RB1 gene were identified: G→T(GGA→TGA)/Gly86stop; delTT(ACTTGG→ACGG)/CODON76～77; C→T(CAT→TAT) /His129Tyr; TT→A(ATTCCT→ATACT)/codon369-370. Combined with previous reports, we identified a total of 21 mutations, emitting 11 exons and 3 introns. 85% of the mutations formed a truncated protein, and 95% of the mutations affected the RB protein (pRB) large-pocket steric structure. The proportion of point mutations was the highest (52%); although the proportion of complex mutations was only 10%, it was much higher than the proportion reported abroad (2%). Conclusion: The RB1 gene mutations in Chinese and Japanese RB patients are mainly subtle mutations and are distributed in many different exons, and most of them seriously affect the normal function of pRB. Mutation methods are focused, the proportion of complex mutations is relatively high, and there is a certain ethnic specificity.