Multiple endocrine neoplasia type 1 is an autosomal dominant cancer syndrome characterized by pituitary, parathyroid and enteropancreatic endocrine tumors, which is caused by germline mutations of the tumor suppressor gene MEN1. In the case reported here, the patient had family with this disease whose germline MEN1 mutation was undetectable by conventional sequencing analysis. Further investigations involving polymorphism analyses, gene dose assay and nucleotide sequencing identified a large germline deletion of approximately 29 kilobase pairs spanning the whole MEN1 gene. The deletion was flanked by Alu repetitive sequences, suggesting unequal homologous recombination as the deletion mechanism. The polymorphism linkage data suggested that an asymptomatic son of the proband did not carry the family mutation. More direct evidence was obtained by gene dose assay and deletion-specific polymerase chain reaction, which demonstrated the normal MEN1 gene dosage and the absence of the deletion breakpoints in this asymptomatic subject and thus definitely excluded the possibility of disease predisposition.

译文

多发性内分泌肿瘤1型是一种常染色体显性显性癌症综合征,其特征是垂体,甲状旁腺和肠胰腺内分泌肿瘤,由抑癌基因men1的种系突变引起。在此处报道的病例中,患者患有该疾病的家族,其生殖系MEN1突变无法通过常规测序分析检测到。涉及多态性分析,基因剂量测定和核苷酸测序的进一步研究确定了跨越整个MEN1基因的大约29千碱基对的大量种系缺失。缺失的两侧是Alu重复序列,表明不相等的同源重组是缺失机制。多态性连锁数据表明,先证者的无症状儿子没有携带家族突变。通过基因剂量测定和缺失特异性聚合酶链反应获得了更直接的证据,这表明该无症状受试者的正常MEN1基因剂量和缺失断点的缺失,因此明确排除了疾病易感性的可能性。

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