Szijan I, Lohmann D R, Parma D L, Brandt B, Horsthemke B
Institut für Humangenetik, Universitätskinikum Essen, Germany.
J Med Genet. 1995 Jun;32(6):475-9. doi: 10.1136/jmg.32.6.475.
Hereditary predisposition to retinoblastoma is caused by germline mutations in the RB1 gene. Most of these mutations occur de novo and differ from one patient to another. DNA samples from 10 families with a child presenting sporadic bilateral retinoblastoma have been analysed for the causative mutation. Using intragenic DNA polymorphisms we detected large deletions in two patients. Heteroduplex and DNA sequence analysis of PCR products from each exon and the promoter region showed small mutations in four patients: a C to T transition in exon 18; 1 bp and 2 bp deletion in exons 20 and 19 respectively; and a 4 bp insertion in exon 7. All these mutations are likely to result in premature termination of transcription. In one of these families, an unaffected carrier was detected. This emphasises the importance of detection of the causative mutation for predictive diagnosis in families with sporadic bilateral retinoblastoma.
视网膜母细胞瘤的遗传易感性是由RB1基因的种系突变引起的。这些突变大多是新发的，且在不同患者之间存在差异。我们对10个有儿童患散发性双侧视网膜母细胞瘤的家庭的DNA样本进行了致病突变分析。利用基因内DNA多态性，我们在两名患者中检测到大片段缺失。对每个外显子和启动子区域的PCR产物进行异源双链和DNA序列分析，发现四名患者存在小的突变：外显子18中的C到T转换；外显子20和19中分别有1个碱基对和2个碱基对的缺失；外显子7中有4个碱基对的插入。所有这些突变都可能导致转录提前终止。在其中一个家庭中，检测到一名未受影响的携带者。这强调了在散发性双侧视网膜母细胞瘤家庭中检测致病突变对于预测诊断的重要性。
