Abstract

Spinocerebellar Ataxia (SCA) is a heterogeneous adult-onset disorder with an autosomal dominant inheritance pattern mainly caused by triplet repeat expansions. Clinical diagnosis of SCA is based on phenotypic features followed by confirmation through molecular diagnosis. To identify status of repeat range in Indian SCA cases and provide extended family screening, we enrolled 70 clinical SCA suspects. For molecular diagnosis, multiplex PCR (M-PCR) was used for common Indian SCA subtypes 1, 2, 3, 6, 7, 10, 12 and 17. TP-PCR was further used in SCA2, 7 and 10 to identify larger expansions. Eighteen out of 70 SCA suspects (25%) were found to be positive for various SCA subtypes- (5 SCA1 (28%), 6 SAC2 (34%), 2 SCA3 (12%), 3 SCA7 (16%) and one each for SCA6 (1%) and SCA17 (1%) subtypes). Genetic counselling and extended family screening were offered to all positive cases and yielded additional nine cases. We have established M-PCR and TP-PCR to detect the CAG repeat expansion in SCA suspects. This method can confirm SCA subtypes in a reliable, rapid and cost-effective way. Genetic characterization of SCA-related genes has great clinical relevance, as it could provide additional information and guidance to clinicians and family members regarding prognosis.

摘要

脊髓小脑性共济失调 (SCA) 是一种异质性成人发病疾病，具有常染色体显性遗传模式，主要由三联体重复扩增引起。SCA的临床诊断基于表型特征，然后通过分子诊断进行确认。为了确定印度 SCA 病例的重复范围状态并提供大家庭筛查，我们招募了 70 名临床 SCA 嫌疑人。对于分子诊断，多重 PCR (M-PCR) 用于常见的印度 SCA 亚型 1、2、3、6、7、10、12 和 17。TP-PCR 进一步用于 SCA2、7 和 10 以识别更大的扩增. 发现 70 名 SCA 嫌疑人中有 18 名 (25%) 对各种 SCA 亚型呈阳性 - (5 名 SCA1 (28%)、6 名 SAC2 (34%)、2 名 SCA3 (12%)、3 名 SCA7 (16%) 和 1 名SCA6 (1%) 和 SCA17 (1%) 亚型）。为所有阳性病例提供了遗传咨询和大家庭筛查，并产生了另外 9 个病例。我们已经建立了 M-PCR 和 TP-PCR 来检测 SCA 嫌疑人中的 CAG 重复扩增。该方法可以可靠、快速且经济高效的方式确认 SCA 亚型。SCA 相关基因的遗传特征具有很大的临床相关性，因为它可以为临床医生和家庭成员提供有关预后的额外信息和指导。