多發性內分泌腫瘤第一型基因診斷

Abstract

主旨: 多發性內分泌腫瘤第一型是一個內分泌方面的腫瘤, 包括有副甲狀腺瘤, 腸胰腺瘤, 腦下腺瘤等內分泌組織的腫瘤。而這個腫瘤在遺傳學上屬於體染色體顯性遺傳。並且已經知道其遺傳被MEN1基因所控制, MEN1基因位於染色體11q13的位置。最近有一篇研究是以台灣地區為範圍, 對疑似多發性內分泌腫瘤第一型患者的MEN1基因加以定序, 以決定是否為此基因突變所致。 設計: 取得台灣地區一位疑似多發性內分泌腫瘤第一型病患的DNA, 她在臨床上表現出副甲狀腺瘤, 以及腦下垂體瘤。我們對MEN1基因基予以定序, 再加上病人所表現的臨床症狀以及家族史, 和之前研究台灣地區多發性內分泌腫瘤第一型的結果做比較。 結果: 我們檢視exon2~10, 並沒有發現哪一個exon有突變發生, 而環顧病人的臨床症狀和家族史, 本案例之病人屬於non-MEN1 gene mutation這一類。 另外特別之處, 乃是exon9在第70~72bp, 兩股遺傳密碼分別為GAT;GAC, 因為轉譯之後都是表現asparate, 在胜肽的層次上不算是突變。而考慮在DNA的層次上, 應該算是多形性變異 (polymorphism)。 結論: 雖然本研究結果為陰性反應, 但依據文獻探討指出: 多發性內分泌腫瘤第一型病患其MEN1基因檢測高達25%呈現陰性反應。此一類病人歸於non-MEN1 gene mutation, 基於和類多發性內分泌腫瘤 (MEN-like syndrome ; MENX) 有著相似的表現型 ( phenotype) , 且類多發性內分泌腫瘤 (MEN-like syndrome ; MENX) 的致病機轉已被許多文獻所揭露, 而這是我們接下來所要努力的方向。

Abstract Objective: Multiple Endocrine Neoplasia Type 1 (MEN1) is a syndrome of endocrine tumor, including parathyroid tumor, entero-pancreatic tumor, and pituitary endocrine tumor. It’s inheritance is autosomal dominant and controlled by the MEN1 gene which was located at chromosome 11q13. Recently, there was one study on the genes of MEN1 patients in Taiwan. This study aimed to exam the DNA sequence of MEN-1 gene in one patient to investigate whether mutations in MEN-1 is responsible for the phenotypes. Design: A patient we chosed had parathyroid tumor and pituitary tumor. We examined the sequence of MEN-1 gene by genomic DNA sequencing. The patient’s clinical symptoms, signs and her pedigree should be also taken into consideration. These results were compared with the previous finding about MEN1 in Taiwan. Results: No mutation was found in exons2~10. Nonetheless, at the70th ~ 72th base pair, the exon9 was found with two inherited codons—GAT and GAC respectively. Both codons encode amino-acid: aspirate. This is not considered a mutation. Moreover, at the level of DNA, we may refer it as polymorphism. Conclusion: Although the research result is negative, according to literature review, there were 25% of gene test of the MEN1 patients found negative. The group of non-MEN1 gene mutation with gene test negative is maybe attributed to MEN-like syndrome (MENX). The mechanism of MEN-like syndrome (MENX) was understood gradually. This will be one direction for futher investigation.