A family of MEN1 with a novel germline missense mutation and benign polymorphisms.
A family of MEN1 with a novel germline missense mutation and benign polymorphisms.
复制标题
具有新型种系错义突变和良性多态性的 MEN1 家族。
作者：
A. Miyauchi;M. Sato;S. Matsubara;H. Ohye;M. Kihara;K. Matsusaka;A. Nishitani;J. Takahara
负责多发性内分泌瘤1型（MEN1）的基因最近已被克隆，其种系突变在患有这种综合征的患者中被鉴定。大多数突变，移码突变或无义突变，预期会导致基因产物menin功能丧失。由于不太常见的错义或框内缺失突变的后果尚不清楚，因此有必要仔细判断此类突变在MEN1疾病中的作用。在这里，我们描述了一个大的多代MEN1家族与一个新的种系错义突变和三个良性多态性。先证者是一名患有甲状旁腺功能亢进和胸腺类癌的男性。我们进行了生化研究和MEN1基因的DNA分析，同时和独立的家庭筛选研究。包括先证者在内的7例患者均携带E45G杂合性错义突变，5例生化检查正常的患者均未携带E45G杂合性错义突变。在50名正常志愿者中未观察到这种突变。因此，这种新的错义突变几乎决定性地导致了这种疾病。尽管本研究中所有突变基因携带者都已患有临床疾病，但对处于风险中的年轻个体进行MEN1基因分析对于在症状发作前识别携带者非常有用。
The gene responsible for multiple endocrine neoplasia type 1 (MEN1) has recently been cloned, and its germline mutations were identified in patients with this syndrome. The majority of the mutations, frameshift or nonsense mutations, are expected to result in a loss of function of the gene product menin. Since the consequence of less common missense or in-frame deletion mutations is not clear, careful judgment is necessary regarding the role(s) of such mutations in MEN1 disease. Here we describe a large multigenerational MEN1 family with a novel germline missense mutation and three benign polymorphisms. The proband was a man with hyperparathyroidism and thymic carcinoid. We performed biochemical studies and DNA analyses of the MEN1 gene simultaneously and independently as family screening studies. Seven patients including the proband were identified, and all of them carried a heterozygous germline missense mutation E45G, but 5 members with normal biochemical results did not. This mutation was not observed in 50 normal volunteers. This novel missense mutation is therefore almost conclusively responsible for the disease. Although all of the mutant gene carriers in the present study already had clinical diseases, an MEN1 gene analysis in younger individuals at risk would be very useful in identifying carriers before the onset of the symptoms.
将遗传性甲状旁腺功能亢进症和催乳素瘤 (MEN1Burin) 基因映射到 11q 染色体：纽芬兰患者中创始人效应的证据。
影响因子：
9.8
作者：
Petty,EM;Green,JS;Marx,SJ;Taggart,RT;Farid,N;Bale,AE
通讯作者：
Bale,AE