Hamaguchi K, Nguyen D C, Yanase T, Ikuyama S, Goto K, Takayanagi R, Nawata H, Kusuda Y, Fukagawa K, Sakata T
Department of Internal Medicine I, Oita Medical University School of Medicine, Japan.
J Hum Genet. 1999;44(1):43-7. doi: 10.1007/s100380050105.
Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant disorder characterized by tumors of the parathyroid glands, the pancreatic islet cells, and the anterior pituitary. Germline mutations of the MEN1 gene in three independent Japanese cases with MEN1 were analyzed. Case 1 has revealed a 2-bp (TA) insertion at nucleotide position 341 (341insTA) in exon 2, which shifts the reading frame such that the mutant protein has a completely different amino acid sequence from codon 78 to the premature stop codon at 119. In case 2, a nucleotide substitution, i.e., TAG in place of TGG, which encodes tryptophan at codon 198 was identified (nonsense mutation). These mutations were heterozygously present and have not been reported previously. Case 3 showed no mutations in the protein-coding exons and exon-intron junctions of the MEN1 gene by single-strand conformation polymorphism or direct sequencing of the polymerase chain reaction (PCR) fragments. We confirmed the finding that patients with MEN1 carry heterozygous germline mutations in the MEN1 gene, which is compatible with the idea that the MEN1 gene is a tumor suppressor gene. The reason why mutations in the coding region of the MEN1 gene could not be detected by PCR-based analysis in some of the MEN1 patients, e.g. case 3, needs to be clarified further.
多发性内分泌腺瘤1型（MEN1）是一种常染色体显性疾病，其特征为甲状旁腺、胰岛细胞和垂体前叶发生肿瘤。我们分析了3例日本MEN1独立病例中MEN1基因的种系突变。病例1在第2外显子的核苷酸位置341处发现有2个碱基对（TA）插入（341insTA），这使得阅读框发生移位，导致突变蛋白从第78密码子开始就具有与野生型完全不同的氨基酸序列，直至119位的提前终止密码子。病例2中，发现了一个核苷酸替换，即第198密码子处编码色氨酸的TGG被TAG取代（无义突变）。这些突变以杂合形式存在，且此前未见报道。病例3通过单链构象多态性分析或聚合酶链反应（PCR）片段直接测序，未在MEN1基因的蛋白质编码外显子和外显子 - 内含子连接区发现突变。我们证实了MEN1患者在MEN1基因中携带杂合种系突变这一发现，这与MEN1基因是肿瘤抑制基因的观点相符。对于某些MEN1患者（如病例3），基于PCR的分析未能检测到MEN1基因编码区突变的原因，还需要进一步阐明。
