Genetic and clinical characteristics of Taiwan maturity-onset diabetes of the young (MODY) patients

年輕人成人型糖尿病(maturity-onset diabetes of the young, MODY)的患者雖然只佔所有糖尿病的2~5%，但是單基因體染色體顯性遺傳模式，可以讓患者家屬評估自身罹病風險、血糖管控及提早預防糖尿病併發症，也可讓醫護人員及患者本身根據特定的基因型差異而在一定程度內預估疾病的可能病程。目前已知有九個不同基因發生突變會導致MODY，也因此依照致病基因的不同又將MODY細分成九個亞型。根據過去文獻，歐洲的家族性MODY患者大約有70~80%能找到突變點，但是亞洲的患者能找到的機會卻不到20%，在台灣甚至只有一名個案找到突變點，但這是否就真的代表台灣地區的發生率，值得做深入性的探討。本研究收集四個MODY家族，再加上另一個還沒有篩檢過CEL、KLF11、PAX4基因的個案，共五名，以直接定序法進行MODY基因篩檢，結果在一名16歲就發病的女性MODY個案找到heterozygous HNF1αP379fsdelCT突變(MODY3)，追查其他家人的基因型發現，個案的父親與妹妹都帶有heterozygous HNF1αP379fsdelCT 突變，但臨床症狀卻比個案輕微，顯示在同一個家族中，基因表現仍受到許多其他因素影響。另外在一名13歲發病的男性個案找到heterozygous CEL D504H變異(MODY8)，但因為CEL基因與MODY疾病的相關研究還不多，此變異點是否真的就是此患者的致病基因還需要進一步的研究討論。 本研究結果不僅提供台灣MODY患者新的基因檢測資訊，在MODY3個案臨床症狀紀錄也有一些更新，希望對MODY患者在基因檢測與遺傳諮詢方面有所幫助。In diabetes, only 2-5% is maturity-onset diabetes of the young (MODY), single gene autosomal dominant inheritance diseases. According to the inheritance, patients and family members could assess their risk, monitor the blood sugar regularly and prevent diabetes complications early. Moreover, the health care workers and the patients can expect course of the disease within possible extent by different genotypes. To date, mutations in nine genes were identified to cause MODY, and subdivided into nine subtype of MODY. From the literatures, patients with family history of MODY in Europe, mutations can be found in 70 - 80%. However, mutations can be found in no more than 20% of the patients in Asia. In Taiwan, only one case was reported. But is this really the prevalence of MODY in Taiwan? In this study, we include 4 cases of MODY, and another case without any mutation in MODY1 - 6, totally 5 cases. By screening 9 MODY genes using direct sequencing, we found a case who had diabetes at 16 year old carries a heterozygous HNF1αP379fsdelCT mutation, her father and sister have the same mutation but with much milder clinical symptoms. And another boy who had onset at 13 years old has heterozygous CEL D504H variant. We are not sure whether the variant is a mutation yet, because there is no functional study or frequency report about this point. This study not only provided new information of MODY genotypes in Taiwan, but also the novel clinical record of a MODY3 case. This study would help improve genetic testing and counseling of MODY