Mitter Diana, Rushlow Diane, Nowak Inga, Ansperger-Rescher Birgit, Gallie Brenda L, Lohmann Dietmar R
Institut für Humangenetik, Universitätsklinikum Essen, Hufelandstr. 55, Essen, 45122, Germany.
Fam Cancer. 2009;8(1):55-8. doi: 10.1007/s10689-008-9198-4. Epub 2008 May 29.
Retinoblastoma (Rb) is initiated by germline mutations in the RB1 gene. Up to date, no mutation was identified in exons 26 and 27. We have identified a 2 bp frameshift insertion in exon 27 of the RB1 gene (RBg.177008_177009dup) in a boy with unilateral Rb and his healthy father that has occurred de novo on the allele transmitted by the father's father. RT-PCR showed that the mutant +2 bp transcript is present in RNA from peripheral leukocytes after short-term culture. The level of the mutant transcript was low compared to the normal transcript indicating abnormal expression of the variant allele. The mutant transcript was further reduced after puromycin treatment suggesting that NMD is not involved. Although oncogenic mutations in the terminal exons of the RB1 gene are rare molecular testing is important as those terminal mutations can be associated with incomplete penetrance and cause high recurrence risk in family members.
视网膜母细胞瘤（Rb）由RB1基因的种系突变引发。截至目前，外显子26和27中未发现突变。我们在一名单侧视网膜母细胞瘤男孩及其健康父亲的RB1基因外显子27中鉴定出一个2 bp的移码插入（RBg.177008_177009dup），该突变是由男孩祖父传递的等位基因上的新生突变。逆转录聚合酶链反应（RT-PCR）显示，短期培养后，外周血白细胞RNA中存在突变的+2 bp转录本。与正常转录本相比，突变转录本的水平较低，表明变异等位基因表达异常。嘌呤霉素处理后，突变转录本进一步减少，提示无义介导的mRNA降解（NMD）未参与其中。虽然RB1基因末端外显子中的致癌突变很少见，但分子检测很重要，因为这些末端突变可能与不完全外显有关，并导致家庭成员的高复发风险。
