泛自閉症障礙(Autism spectrum disorder, ASD) 是指患有社交能力缺損、溝通障礙和行為異常的神經發展障礙疾患的總稱。這些疾患包括了自閉症、雷特氏症、兒童期崩解性疾患、亞斯柏格症與其它未註明之廣泛性發展疾患。泛自閉症障礙的盛行率約為千分之六，它的致病原因到目前為止仍不是很清楚。而泛自閉症障礙的遺傳性高達64%以上，故推測遺傳因子的影響是造成這個疾病的主要原因之一。泛自閉症障礙是一種複雜的遺傳性疾病，已經有許多研究指出它具有高度的基因異質性，這也使得泛自閉症障礙的研究工作相對的更顯困難。目前來說，連鎖分析和遺傳相關性分析是有效的方法來找出泛自閉症障礙患者的候選基因區段，並且比較候選基因在病人與常人之間的差異。但這兩個方法皆受限於需要足夠的樣本數量才可得到具有統計意義的結果。細胞遺傳學則是另一個方法，直接針對泛自閉症患者的染色體進行分析，以找到可能的候選基因區段。在此研究中，我們利用染色體G條紋染色法(G banding) 去分析69位泛自閉症患者周邊血液細胞中的染色體，期望能發現染色體異常以找出與此疾患相關的候選基因區段。每個病例皆分析20顆細胞，最後分析的結果顯示有2個病例具有染色體異常。第一個病例是在20顆細胞中發現有11顆細胞第15號染色體長臂12的區段發生了缺失(Deletion on chromosome 15q12)。第二個病例則是在20顆細胞中發現有7顆細胞第2號染色體短臂11.2到長臂14.2區段發生染色體倒轉(Inversion on chromosome 2p11.2-q14.2)。這二個異常區段在未來可進一步利用分子遺傳學方法找出斷點位置，並更精確的定出缺失片段的大小，期望將來可以此區段做為候選基因區段，針對此區段所含的基因進行遺傳相關性分析與家族性的研究。

Autism spectrum disorder (ASD) is the general name of a group of childhood-onset neurodevelopmental disorder with impairments in social interaction and communication, as well as abnormal behavior. ASD includes autism, Rett’s disorder, Childhood disintegrative disorder, Asperger’s disorder, and pervasive developmental disorder not otherwise specified (PDD-NOS). The prevalence of ASD is estimated to be 6.0-6.5 in 1000, but the etiology is not clear yet. The heritability of ASD is more than 64%, so genetic factor plays a major role in the etiology of this disease. ASD is a complex genetic disease, and previous studies suggest ASD displays a high degree of genetic heterogeneity, which makes ASD research relatively difficult. At present time, linkage analysis and association study are useful methods to find out the candidate regions involved, but both methods are limited by the sample size. Cytogenetic method is the other choice to find candidate regions on the chromosome of ASD patients. In this study, we have performed chromosomal analysis using the G-banding technique on 69 patients with ASD. We analyzed 20 cells in each case, and we identified 2 ASD cases having chromosome structural abnormalities. One patient has 11 out 20 cells were found to have deletion of 15q12. Another one has chromosomal mosaicism: 7 out of 20 cells were found to have chromosome 2p11.2-q14.2 inversion. The authenticity of these regions need further confirmation by fluorescent in situ hybridization (FISH), and the breakpoints and the deleted size need further delineation by array-based comparative genomic hybridization.

誌謝....................................................I
英文摘要................................................II
中文摘要................................................IV
目錄....................................................VI
緒論....................................................1
實驗目的................................................11
材料與方法..............................................12
結果....................................................20
討論....................................................23
圖表....................................................29
參考文獻................................................40

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