臺灣博碩士論文加值系統

Usher氏症候群第二型為體染色體隱性遺傳疾病，亦為此症候群中比例最高之臨床類型，其病徵為合併先天性中至重度感音神經性聽力損失與漸進式色素性網膜炎，目前於人類染色體中已發現四個基因座與其具直接關聯性，其中以USH2A基因突變致病比例最高，但因人種背景不同於該基因之致病位點與常見致病位點皆有所不同，故本研究以一個台灣地區含有兩位符合Usher氏症候群第二型臨床病徵之病人及其家屬共11人之家族，以直接定序之方式，檢測USH2A異型體B基因中可轉譯胺基酸之外顯子，於本研究家族中發現15個多型性位點與2個新致病突變位點，其中13個多型性位點與前人以東亞地區人種為研究對象之發表相同，兩個新致病位點一為停止轉譯胺基酸之位點c.2187C>A與一刪除式位點c.13852delG，在本家族中為複異型結合突變型式；本研究結果顯示台灣本型病人之USH2A組成應與非東亞地區人種較為不同，而本研究之發現除可供病人臨床診斷與後續病情追蹤參考，並可供未來用於臨床診斷工具與相關疾病治療之研發。

Usher syndrome type II (USH2), an autosomal recessive disorder, is the most common type of User syndrome and characterized by congenital moderate to severe sensorineural hearing loss and progressive retinitis pigmentosa. Up to date, there are 4 loci associated with USH2. Defects in the USH2A gene have been responsible for most cases of USH2, but the locations and frequency of mutation sites are different between ethnicities. In this report, we screened the entire coding region of USH2A isoform B for a Taiwan family with 2 USH2 patients and 9 relatives by direct sequencing, and uncovered 17 different sequence variations, including 15 polymorphism sites and 2 novel mutations. Thirteen of 15 polymorphism sites have been reported in previous publications related to Eastern Asian populations and 2, c.997T>C and c.7448T>G, are novel. The 2 novel mutations, c.2187C>A (p.C729X) and c.13852delG (p.A4618fs), are compound heterozygotes in this family. Our results indicate that the mutation spectrum of USH2A gene among Taiwan population may differ from non-Eastern Asian populations. The finding of the report provides information not only for clinical diagnoses and follow up patients of this family in the future but also for the development of novel clinical diagnoses tools and therapies.

中文摘要 ii
ABSTRACT iii
緒論 1
研究動機 1
研究重要性 2
研究目的 3
文獻查證 5
聽損之原因與型式 5
遺傳性聽損 6
Usher氏症候群 7
Usher氏症候群與分子遺傳層面相關研究 9
USH2A基因之分子遺傳學研究 10
研究方法 15
參與成員 15
研究進行場所 16
引子設計與合成 16
參與者DNA之萃取 17
片段放大 18
定序反應 19
定序資料整理與分析 22
研究結果與討論 24
聚合酶連鎖反應與定序反應使用引子 24
序列改變位點 25
致病之突變位點 29
研究結論與建議 34
結論 34
建議 35
研究貢獻 37
參考文獻 38
附錄一 66

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