- 學位論文
X染色體脆折症帶因者篩檢-台灣經驗
Carrier Screening for Fragile X Syndrome in Taiwan
摘要
X染色體脆折症（Fragile X Syndrome, FXS）為最常見的遺傳性智能障礙疾病，約250位女性中有1位為X染色體脆折症帶因者，而母親CGG重複次數越多，將異常擴增遺傳給下一代患病機率則越高。 為統計漢人族群準突變及全突變帶因者發生率分析產前篩檢可行性、成本效益、優勢，本研究資料蒐集自2014年09月至2017年10月份共23,468位成年女性及其帶因者下一代之X染色體脆折症結果。以周邊血液進行DNA萃取後以商業化的試劑組進行聚合酶鏈鎖反應檢測FMR1基因CGG重複次數。 結果顯示最常見的等位基因（Allele）為29次重複（39.75%），其次為30次（25.36%）及28次（8.59%）。32位準突變帶因者，其中19次懷孕（52.8%）將異常擴增等位基因遺傳給下一代，而擴增為全突變則有6次。而有9位母親CGG重複次數大於69並將異常擴增等位基因遺傳給下一代，且擴增為全突變有6次。一名無症狀的全突變女性具有280次CGG重複的等位基因，第一胎產前檢測胎兒結果為5’UTR和第一外顯子具缺失的男性而中止妊娠，第二胎則為全突變女性胎兒。另一名無症狀的5’UTR和未知CGG重複序列上游缺失女性，其男性胎兒遺傳了此缺失等位基因而中止妊娠。 各族群FXS流行率皆不同，在此建立了漢人族群最大的帶因者篩檢研究，無症狀的準突變及全突變女性的聯合帶因率為0.14%（1/711），也為台灣的產前遺傳諮詢提供了相當重要的數據。
並列摘要
Fragile X syndrome (FXS) is the most common cause of inherited intellectual and developmental disability. Approximately 1 in 250 females are carriers. The risk of transmitted from mother to offspring appear to be related to the size of the CGG repeat, with the highest risk associated with larger repeats. Survey the prevalence of FXS Premutation (PM) and Full mutation (FM) carriers and the cost-effectiveness of the prenatal screening of FXS in a large Han Chinese cohort. This was a retrospective observational study including 23,468 Chinese women and offspring of carrier mothers between September 2014 and October 2017. The FMR1 CGG repeat status was determined using commercialized CGG repeat primed PCR with DNA extracted from peripheral blood. In our cohort, the most prevalent allele was 29 repeats (39.75%), followed by 30 (25.36%) and a minor allele was 28 repeats (8.59%). We identified 32 women with PM. The PM allele was transmitted to the fetus in 19 pregnancies (52.8%), and six of these 19 expanded to FM. Six of the nine maternal alleles that exceeded 69 repeats expanded to FM. One asymptomatic woman was found to have a FM allele with 280 CGG repeats. Her first pregnancy was terminated because prenatal genetic diagnosis revealed a male fetus carrying a FMR1 gene deletion of 5' UTR and exon 1. Her second fetus was a female carrying a FM allele as well. One asymptomatic women had a deletion of partial 5‘ UTR and upstream of unknown CGG repeats of FMR1 gene. The male fetus had inherited the deleted allele and was terminated. Population-based prevalence of FXS varied in countries. This is the largest study of the FXS carrier screening in Chinese women. The combined prevalence of PM and FM of FXS in normal asymptomatic Taiwanese women was as high as 0.14% (1 in 711) in this study. The reported FXS carrier rate in Taiwan is important for prenatal counseling.