Goldberg Y, Barnes-Kedar I, Lerer I, Halpern N, Plesser M, Hubert A, Kadouri L, Goldshmidt H, Solar I, Strul H, Rosner G, Baris H N, Peretz T, Levi Z, Kariv R
Sharett Institute of Oncology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
Clin Genet. 2015 Jun;87(6):549-53. doi: 10.1111/cge.12530. Epub 2014 Nov 28.
Diagnosis of Lynch syndrome (LS) may be complex. Knowledge of mutation spectrum and founder mutations in specific populations facilitates the diagnostic process. Aim of the study is to describe genetic features of LS in the Israeli population and report novel and founder mutations. Patients were studied at high-risk clinics. Diagnostics followed a multi-step process, including tumor testing, gene analysis and testing for founder mutations. LS was defined by positive mutation testing. We diagnosed LS in 242 subjects from 113 families coming from different ethnicities. We identified 54 different mutations; 13 of them are novel. Sixty-seven (59%) families had mutations in MSH2, 20 (18%) in MSH6, 19 (17%) in MLH1 and 7 (6%) in PMS2; 27% of the MSH2 mutations were large deletions. Seven founder mutations were detected in 61/113 (54%) families. Constitutional mismatch repair deficiency (CMMR-D) was identified in five families. Gene distribution in the Israeli population is unique, with relatively high incidence of mutations in MSH2 and MSH6. The mutation spectrum is wide; however, 54% of cases are caused by one of seven founder mutations. CMMR-D occurs in the context of founder mutations and consanguinity. These features should guide the diagnostic process, risk estimation, and genetic counseling.
林奇综合征（LS）的诊断可能较为复杂。了解特定人群中的突变谱和始祖突变有助于诊断过程。本研究的目的是描述以色列人群中LS的遗传特征，并报告新的和始祖突变。在高危诊所对患者进行了研究。诊断遵循多步骤流程，包括肿瘤检测、基因分析和始祖突变检测。LS通过阳性突变检测来定义。我们在来自不同种族的113个家庭的242名受试者中诊断出LS。我们鉴定出54种不同的突变；其中13种是新的。67个（59%）家庭的MSH2基因发生突变，20个（18%）家庭的MSH6基因发生突变，19个（17%）家庭的MLH1基因发生突变，7个（6%）家庭的PMS2基因发生突变；MSH2突变中有27%是大片段缺失。在61/113（54%）个家庭中检测到7种始祖突变。在5个家庭中发现了遗传性错配修复缺陷（CMMR-D）。以色列人群中的基因分布是独特的，MSH2和MSH6基因的突变发生率相对较高。突变谱很广；然而，54%的病例是由7种始祖突变之一引起的。CMMR-D发生在始祖突变和近亲结婚的背景下。这些特征应指导诊断过程、风险评估和遗传咨询。
