Lynch syndrome is an inherited cancer predisposition syndrome caused by germline defects in any of the mismatch repair (MMR) genes. Diagnosis of carriers makes precision prevention, early detection, and tailored treatment possible. Herein we report a novel founder deletion of 18,758 bp, mediated by Alu repeats on both sides, detected in Ethiopian Jews. The deletion, which encompasses exon 9–10 of the MSH2 coding sequence, is associated mainly with early-onset MSH2/MSH6-deficient colorectal cancer (CRC) and liposarcoma. Testing of 35 members of 5 seemingly unrelated families of Ethiopian origin yielded 10/21 (48%) carriers, of whom 9 had CRC. Age at first tumor diagnosis ranged from 16 to 89 years. Carriers from the oldest generations were diagnosed after age 45 years (mean 57), and carriers from the younger generation were diagnosed before age 45 years (mean 30). Awareness of this founder deletion is important to improve patient diagnosis, institute surveillance from an early age, and refer patients for genetic counseling addressing the risk of bi-allelic constitutional MMR deficiency syndrome.

林奇综合征是一种遗传性癌症易感性综合征，由任何错配修复 (MMR) 基因中的种系缺陷引起。携带者的诊断使精准预防、早期发现和量身定制的治疗成为可能。在这里，我们报告了一个 18,758 bp 的新创始人缺失，由两侧的Alu重复介导，在埃塞俄比亚犹太人中检测到。缺失，包括MSH2的外显子 9-10编码序列主要与早发性 MSH2/MSH6 缺陷型结直肠癌 (CRC) 和脂肪肉瘤相关。对 5 个看似无关的埃塞俄比亚血统家庭的 35 名成员进行的测试产生了 10/21 (48%) 的携带者，其中 9 人患有 CRC。首次肿瘤诊断的年龄范围为 16 至 89 岁。最老一代的携带者在 45 岁（平均 57 岁）之后被诊断出来，而年轻一代的携带者在 45 岁之前被诊断出来（平均 30 岁）。意识到这种创始人缺失对于改善患者诊断、从小开始监测以及转诊患者进行遗传咨询以解决双等位基因构成性 MMR 缺乏综合征的风险非常重要。