Felton K E A, Gilchrist D M, Andrew S E
Department of Medical Genetics, University of Alberta, Edmonton, Alberta, Canada.
Clin Genet. 2007 Jun;71(6):483-98. doi: 10.1111/j.1399-0004.2007.00803.x.
Mutations in the DNA mismatch repair (MMR) genes are associated with the inheritance of hereditary non-polyposis colorectal cancer, also known as Lynch syndrome, a cancer syndrome with an average age at onset of 44. Individuals presenting with colorectal cancer are diagnosed with Lynch I, whereas individuals who present with extra-colonic tumors (such as endometrial, stomach, etc.) are identified as patients with Lynch syndrome II. Recently, 30 families have been reported with inheritance of biallelic mutations in the MMR genes. Here we summarize the phenotype of individuals with inheritance of homozygous or compound heterozygous mutations in the MMR genes that result in a complete lack of protein or greatly compromised protein function. In contrast to individuals with Lynch syndrome I and II, individuals with no MMR function present with childhood onset of hematological and brain malignancies, whereas residual MMR function can also result in gastrointestinal cancers and an age of onset in the second to fourth decade. Individuals with biallelic MMR mutations often present with café-au-lait spots, regardless of the level of MMR function remaining. Thus, the inheritance of two MMR gene mutations is a separate entity from Lynch I or II or the subtypes Turcot and Muir-Torre.
DNA错配修复（MMR）基因的突变与遗传性非息肉病性结直肠癌（也称为林奇综合征）的遗传相关，这是一种平均发病年龄为44岁的癌症综合征。患有结直肠癌的个体被诊断为林奇I型，而患有结肠外肿瘤（如子宫内膜癌、胃癌等）的个体被认定为林奇综合征II型患者。最近，已有报道30个家族存在MMR基因双等位基因突变的遗传情况。在此，我们总结了MMR基因纯合或复合杂合突变遗传个体的表型，这些突变导致蛋白质完全缺失或功能严重受损。与林奇综合征I型和II型个体不同，MMR功能缺失的个体在儿童期就会出现血液系统和脑恶性肿瘤，而残余的MMR功能也可导致胃肠道癌症，发病年龄在第二至第四个十年。无论剩余的MMR功能水平如何，双等位基因MMR突变的个体通常会出现咖啡牛奶斑。因此，两个MMR基因突变的遗传是一个独立于林奇I型或II型或Turcot和穆尔-托雷亚型的实体。
