建立台灣年輕型糖尿病遺傳諮詢之模式

Abstract

早發型糖尿病(maturity onset diabetes of the young, MODY)是一種自體顯性遺傳疾病，並已知至少有六個不同基因發生突變時會導致MODY發生。其中一個基因和醣解酵素(glucokinase, GCK)有關，此為MODY2，另外五個是和轉錄因子有關：hepatocyte nuclear factor (HNF)4α和MODY1相關，HNF1α和MODY3相關，HNF1β為MODY5，還有insulin promoter factor 1 (IPF-1)為MODY4，及neurogenic differentation factor 1 (NeuroD1)為MODY6。這些突變皆可導致β細胞功能不全及糖尿病。MODY病人和其他第2型糖尿病人間有些不同的臨床表徵，包括有：MODY至少有二代或是更多代之間是具有明顯的家族史、在年紀輕時就有病徵及非肥胖型。本篇研究目的，是欲了解台灣MODY家族的遺傳型態，建立台灣MODY病人的基因型，並能藉此將對於MODY病人的遺傳諮詢模式做一探討。目前收集了一案例，其家族中兩代共有四位罹病者，將未檢測的GCK、HNF4α、HNF1β及IPF-1四個基因之exons做PCR和定序，另外，已知HNF1α基因之exon 9中的一胺基酸改變，在正常人中亦做PCR和定序，但這些基因檢測中，並無發現任何特定或有意義的突變是和MODY的發生有相關，且過去找到的HNF1α基因中之突變亦在正常人中發現，故此應為單一核苷酸多型性。本文個案完成目前已知和MODY相關之基因檢測，且在MODY疾病之遺傳諮詢部分，擬定其基因檢測同意書並探討與設立預測性基因檢測之流程，對於台灣MODY疾病的研究與診斷MODY亞型的模式有一完整的開端，未來可望能再進一步朝其他和胰臟功能或是胰島素分泌相關基因來做分析或檢測。

Maturity onset diabetes of the young (MODY) is a autosomal dominant inheritance disease and the six subtypes are caused by six different genes. The glucokinase (GCK) is associated with MODY 2. The others are transcription factors: hepatocyte nuclear factor-4α (HNF-4α, MODY1), HNF-1α (MODY3), HNF-1β (MODY5), insulin promoter factor 1 (IPF-1, MODY4) and neurogenic differentation factor 1 (NeuroD1, MODY6). The mutations of all these genes lead to the pancreatic β-cell dysfunction and diabetes. The difference in clinical phenotypes between MODY and type 2 diabetes are the transmission of diabetes through at least two generations in a family, ideally two family members diagnosed before 25 years unlike type 2 diabetes, MODY is rarely associated with obesity. Our aim was to initiate a genetic diagnosis and counseling protocol in Taiwan. The case is one of four MODY patients in two generations in the family. Previously, we have examined the HNF-1α and NeuroD1. Thus, the coding regions with intron-exon site of four other genes including GCK, HNF-4α, HNF-1β and IPF-1 were examined by polymerase chain reaction (PCR) and direct sequencing. Besides, four normal elderly control were tested for the mutation found in the exon 9 of HNF-1α before by PCR and direct sequencing. There is no novel mutation within these genes. It is important to set up the format for genetic testing and genetic counseling for MODY in Taiwan.