Neurofibromatosis von Recklinghausen type I phenotype and early onset of cancers in siblings compound heterozygous for mutations in MSH6
Neurofibromatosis von Recklinghausen type I phenotype and early onset of cancers in siblings compound heterozygous for mutations in MSH6
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DOI：
10.1002/ajmg.a.30998
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发表时间：
2005-12-01
影响因子：
2
通讯作者：
Okkels, H
中科院分区：
文献类型：
--
作者：
Ostergaard, JR;Sunde, L;Okkels, H
我们报告一个非血缘家庭，其中两个兄弟姐妹的皮肤表现，导致诊断为神经纤维瘤病I型（NF 1）发展中枢神经系统肿瘤在早期的年龄。此外，其中一人患上了T细胞淋巴瘤。父母都没有NFI。已知母亲为MSH 6突变杂合子，而父亲为不同的MSH 6突变杂合子。对患儿进行MSH 2、MLH 1、MSH 6、PMS 1、PMS 2和MLH 3的筛查，发现他们都是父母MSH 6突变的复合杂合子。最近，大约有十几个其他情况下，遗传性双等位基因缺陷的错配修复（MMR）基因与早发性中枢神经系统肿瘤，血液恶性肿瘤，胃肠道肿瘤，白内障斑，和其他NF-1的功能已被报道。在本研究中，我们suramarize 27个人的临床表现纯合子或复合杂合子的MMR基因突变的医学文献报道。我们认为，双亲遗传突变的MMR基因之一，应考虑在儿童与多个多发性斑痣谁有早发性中枢神经系统肿瘤，血液恶性肿瘤，或早发性胃肠道肿瘤。(c)2005 Wiley-Liss，Inc.
We report on a nonconsanguineous family in which two siblings with cutaneous manifestations leading to a diagnosis of neurofibromatosis type I (NF1) developed CNS tumors at an early age. In addition, one of them developed a T-cell lymphoma. Neither parent had NFl. The mother was known to be heterozygous for a MSH6 mutation, and the father was found to be heterozygous for a different MSH6 mutation. Screening of MSH2, MLH1, MSH6, PMS1, PMS2, and MLH3 in the affected children disclosed that they both were compound heterozygote for the MSH6 mutations of their parents. Most recently, about a dozen other cases of inherited bi-allelie deficiency of mismatch repair (MMR) genes associated with early onset CNS tumors, hematologic malignancy, gastrointestinal neoplasia, cafe-au-lait spots, and other NF1 features have been reported. In the present study, we suramarize the clinical findings of 27 individuals homozygous or compound heterozygous for an MMR gene mutation reported in the medical literature. We suggest that biparentally inherited mutations of one of the MMR genes should be considered in children with multiple cafe-au-lait spots who have early-onset CNS tumors, hematologic malignancies, or early onset gastrointestinal neoplasia. (c) 2005 Wiley-Liss, Inc.