Machado-Joseph Disease簡稱MJD，是一種體染色體顯性的遺傳
性疾病，屬於漸進性神經退化性疾病的一種，主要的臨床表徵為運動障礙
、肌肉萎縮、及錐體系路徑症狀等。調控此症狀的基因座落於第十四對染
色體的長臂上(14q32.1)，稱為MJD基因。造成疾病的原因之一，是由於在
此基因的3''端轉譯區(3''-translated region)內有一段異常的CAG核酸重
複序列發生倍增突變(amplification mutation)。近年來國外有多篇關於
MJD病例的報告，唯獨不見台灣的相關病例，然而我們卻深信台灣應該也
有此類的疾病發生，只是尚未發現。所以為了尋找台灣的MJD病人，首先
從臨床醫師的病歷診斷幫助，再配合實驗室分子生物技術的分析，終於在
國內找到了患有MJD疾病的二大家族。其中有十位為MJD患者(affected)，
另十位是尚無臨床症狀的個體(asymptomatic individuals)但具有CAG擴
增突變，他們的CAG repeats範圍從72-85個repeats，我們同時分析了150
個正常人的染色體，正常範圍是13-44個repeats。本研究中觀察到MJD基
因於分子遺傳學上有幾個特點：一、兩代間的CAG重複序列的遺傳具有不
穩定性。二、父親比母親更影響子代CAG repeats的數目。三、重複序列
的長度會影響發病的年齡。因此偵測病人的家屬是否帶有異常基因甚為重
要。在本實驗中，我們成功的從絨毛細胞中偵測到MJD基因的CAG重複序列
，以優生保健立場而言，這對於日後MJD基因的篩檢及產前診斷具有實質
的意義，所以我們相信這套分生的偵測方法，對臨床醫師在診斷MJD的疾
病將有很大幫助。
Machado-Joseph Disease (MJD) is an
autosomal dominant spinocerebellar degeneration characterized by
cerebellar ataxia and extra pyramidal signs, dystonia with
rigidity, and distal muscular atrophies. The disease locus was
mapped to chromosome 14q32.1 in different origins. Unstable CAG
expansion of the MJD gene was identified as the pathologic
mutation for MJD. We have analyzed 20 MJD individuals from 2
independent MJD families and 150 normal alleles from Taiwan''s
population. The range of the CAG repeat size was 13-44 repeats
in the normal alleles while the MJD alleles contained 72-85
repeats in the present study. In the normal alleles, 16 repeats
units were the most common one. Our results indicated an inverse
correlation between CAG repeats length and age at onset .
Instability of the CAG tract length during transmission from
parent to offspring was observed; both increase and decrease in
size between parents and offspring occur, with larger variations
in paternal than in maternal transmissions. Moreover, we
demonstrated that PCR amplification of the CAG repeats of the
MJD gene from fetal villus was successful. Therefore, the
prenatal screening by the use of genomic PCR will be provided
for the affected families in the future.
