PDF(Pubmed)
Abstract：
Constitutional mismatch repair deficiency (CMMRD) is a rare childhood cancer predisposition syndrome that results from biallelic germline mutations in one of the four MMR genes, MLH1, MSH2, MSH6, or PMS2. This syndrome is characterized by a broad spectrum of early-onset malignancies, including hematologic malignancies, colorectal malignancies, brain tumors, and other malignancies. It is common to have more than one malignancy in an individual diagnosed with CMMRD. In addition to malignancies, primary immunodeficiency in the form of low or absent immunoglobulin levels can also be seen in CMMRD. Congenital abnormalities such as agenesis of the corpus callosum (ACC), cavernous hemangioma, and other non-neoplastic diseases can also be linked to it. In this case report, we discussed the case of a girl born out of consanguineous marriage initially identified as having T-cell acute lymphoblastic lymphoma and later found to have selective immunoglobulin A (IgA) deficiency. Her younger sibling with a pontine cavernous hemangioma was also diagnosed with lymphoma. The girl exhibited brain lesions on magnetic resonance imaging (MRI), which were initially diagnosed as posterior reversible encephalopathy syndrome (PRES) related changes; however, one of the lesions persisted and remained stable over a period of 2 years and more in favor of diffuse glioma. The younger sibling also showed a solitary lesion in the brain. Based on the clinical and radiological findings, a diagnosis of CMMRD was suspected. Next-generation sequence (NGS) analysis of her blood sample was done. The results showed a homozygous mutation in the MSH6 gene was diagnostic of CMMRD.
摘要：
宪法错配修复缺陷（CMMRD）是一种罕见的儿童癌症易感性综合征，由四个MMR基因之一的双等位基因种系突变引起，MLH1、MSH2、MSH6或PMS2。这种综合征的特征是广泛的早发性恶性肿瘤，包括恶性血液病,结直肠恶性肿瘤，脑肿瘤,和其他恶性肿瘤。在被诊断患有CMMRD的个体中通常具有多于一种恶性肿瘤。除了恶性肿瘤,在CMMRD中也可以看到免疫球蛋白水平低或不存在的原发性免疫缺陷。先天性异常，例如call体（ACC）的发育不全，海绵状血管瘤,其他非肿瘤性疾病也可能与之相关。在这个案例报告中,我们讨论了一个女孩的案例，该女孩最初被确定为患有T细胞急性淋巴母细胞淋巴瘤，后来发现患有选择性免疫球蛋白A（IgA）缺乏症。她的弟弟妹妹患有脑桥海绵状血管瘤，也被诊断出患有淋巴瘤。女孩在磁共振成像（MRI）上表现出脑部病变，最初被诊断为可逆性后部脑病综合征（PRES）相关的变化；然而，其中一个病变持续存在，并在2年的时间内保持稳定，更有利于弥漫性神经胶质瘤。年轻的兄弟姐妹在大脑中也显示出孤立的病变。根据临床和放射学发现，怀疑有CMMRD的诊断.对她的血样进行下一代序列(NGS)分析。结果表明，MSH6基因的纯合突变可诊断CMMRD。
