Krishna Nithin, Mohan Surendra, Yashavantha B S, Rammurthy A, Kiran Kumar H B, Mittal Uma, Tyagi Shivani, Mukerji Mitali, Jain Sanjeev, Pal Pramod Kumar, Purushottam Meera
Department of Psychiatry, National Institute of Mental Health & Neuro Sciences, Bangalore, India.
Indian J Med Res. 2007 Nov;126(5):465-70.
BACKGROUND & OBJECTIVE: Spinocerebellar ataxias (SCAs) are often caused by expansions of CTG/ CAG trinucleotide repeat in the genome. Expansions at the SCA1, 2 and 3 loci are the most frequent, but differences in their relative proportion in regions occur across the world. We carried out this study to assess the occurrence of SCA1, 2 and 3, at a tertiary neuro-psychiatric center in Bangalore, Karnataka.
Probands (N=318) who were diagnosed to have an ataxia syndrome (progressive degenerative ataxia of unknown cause) attending the clinical services of the National Institute of Mental Health and Neuro Sciences (NIMHANS), Bangalore, were evaluated over a period of three years. Standard protocols were used for both clinical and molecular diagnosis.
Genotyping established that SCA1, 2 and 3 accounted for more than one third of the ataxia cases seen in the clinic. In the cases with established family history and autosomal dominant inheritance SCA1 was most prevalent followed by SCA2 and SCA3.
INTERPRETATION & CONCLUSION: Our findings suggested SCA1 rather than SCA2 to be the more common mutation in southern India. Large numbers of SCA3 probands were also identified. Differences in prevalence of these syndromes within India need to be explored further for founder effects, correlations with phenotype, and patterns of outcome. Family history was not apparent in almost a fifth of those tested positive, highlighting the value of testing even in the absence of family history. Molecular testing should be extended to cover the other forms of ataxia, of which a large number are now known. Combined efforts to confirm the presence of these less common forms, as well as family studies to detect novel mutations, are necessary in this context in India.
脊髓小脑共济失调（SCAs）通常由基因组中CTG/CAG三核苷酸重复序列的扩增引起。SCA1、2和3位点的扩增最为常见，但它们在不同地区的相对比例存在差异。我们在卡纳塔克邦班加罗尔的一家三级神经精神中心开展了这项研究，以评估SCA1、2和3的发生率。
在三年时间里，对前往班加罗尔国家精神卫生和神经科学研究所（NIMHANS）临床服务部就诊、被诊断患有共济失调综合征（原因不明的进行性退行性共济失调）的318名先证者进行了评估。临床和分子诊断均采用标准方案。
基因分型表明，SCA1、2和3占该诊所所见共济失调病例的三分之一以上。在有明确家族史且为常染色体显性遗传的病例中，SCA1最为常见，其次是SCA2和SCA3。
我们的研究结果表明，在印度南部，SCA1而非SCA2是更常见的突变类型。还发现了大量SCA3先证者。印度境内这些综合征患病率的差异，需要进一步探究其奠基者效应、与表型的相关性以及转归模式。在近五分之一检测呈阳性的患者中未发现明显家族史，这凸显了即使没有家族史进行检测的价值。分子检测应扩大到涵盖其他形式的共济失调，目前已知其中有很多种。在印度这种情况下，有必要共同努力确认这些较不常见形式的存在，并开展家族研究以检测新的突变。
