Nguyen Aurélia, Bougeard Gaelle, Koob Meriam, Chenard Marie Pierre, Schneider Anne, Maugard Christine, Entz-Werle Natacha
Laboratoire de Biochimie et de Biologie Moléculaire, CHRU Hautepierre Strasbourg, 1, Avenue Molière, 67098, Strasbourg, France.
EA 3430, Université de Strasbourg, "Progression tumorale et microenvironnement. Approches translationnelles et épidémiologie", 3, Avenue Molière, 67000, Strasbourg, France.
Fam Cancer. 2016 Oct;15(4):571-7. doi: 10.1007/s10689-016-9894-4.
The constitutional MisMatch Repair deficiency (CMMRD) syndrome is one of the inherited cancer predisposition syndromes. More than two-third patients belonging to a CMMRD family are diagnosed mainly in the first decade with brain cancers and/or hematological malignancies. This syndrome is due to bi-allelic germline mutations in genes of the MMR pathway (MLH1, MSH2, MSH6 or PMS2). Our family report begins with the index case presenting initially with a medulloblastoma, which was even the two relapses in complete remission, when she was diagnosed for an AML. She died after bone marrow transplantation from toxicity. The family history was progressively established when her uncle was diagnosed for a colonic cancer and a cousin for a brain tumor. Surprisingly, her father had an atypical sarcoma but her brother also presented a lymphoma followed by a gliomatosis cerebri. A new MLH1 bi-allelic mutation was identified in this family. More than the diagnostic difficulties, this family report illustrates the complexity of the microsatellite instability detection in CMMRD patients, which has to be discussed further to a more accurate diagnosis in the pediatric setting, and address the question of the proper diagnostic tool to use in such genetic background with hypermutated tumors.
先天性错配修复缺陷（CMMRD）综合征是遗传性癌症易感综合征之一。超过三分之二的CMMRD家族患者主要在第一个十年被诊断出患有脑癌和/或血液系统恶性肿瘤。该综合征是由于错配修复（MMR）途径基因（MLH1、MSH2、MSH6或PMS2）的双等位基因种系突变所致。我们的家族报告始于索引病例，该病例最初表现为髓母细胞瘤，在被诊断为急性髓系白血病（AML）时，甚至在完全缓解期出现了两次复发。她在骨髓移植后因毒性反应死亡。当她的叔叔被诊断出患有结肠癌，一个堂兄弟被诊断出患有脑肿瘤时，家族病史逐渐明晰。令人惊讶的是，她的父亲患有非典型肉瘤，而她的哥哥也患了淋巴瘤，随后发展为大脑胶质瘤病。在这个家族中发现了一种新的MLH1双等位基因突变。除了诊断困难外，这份家族报告还说明了CMMRD患者微卫星不稳定性检测的复杂性，在儿科环境中必须进一步讨论以实现更准确的诊断，并解决在这种肿瘤高度突变的遗传背景下使用何种合适诊断工具的问题。
