Molecular spectrum, family screening and genetic counselling of Spinocerebellar Ataxia (SCA) cases in an Indian scenario.

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.

Molecular spectrum and allelic frequency of different subtypes (1, 2, 3, 6 and 7) of Spinocerebellar ataxia in the Indian population.

Spinocerebellar ataxia (SCA) is a rare, heterogeneous genetic group of disorders with overlapping clinical features that arises as a result of the degeneration of Purkinje cells. The most prominent clinical feature of SCA is difficulty with whole body movements. The aim of the current study was to analyze the allelic frequency of normal repeat sizes in different SCA subtypes in the north Indian population. Blood samples were collected from 200 subjects, DNA was extracted, and then multiplex PCR and fragment analysis were performed using the ABI-310 genetic analyzer. The prevalent cytosine-adenine-guanine (CAG) repeat size or allelic frequency for SCA1, 2, 3 , 6, and 7 were 29 repeats (59%), 21 repeats (72.5%), 23 repeats (13.1%), 9 repeats (30%), and 3 repeats (75%), respectively. Results indicated that the normal repeats are shifting to lower or upper ranges in the Indian scenario, and similar findings have been reported in other previous studies. Thus, this and other studies have suggested that the normal range of repeats for various SCA in the Indian scenario needs to be redefined and should be confirmed by studies with larger samples and by functional studies.

Current molecular insight to reveal the dynamics of CAG repeating units in spinocerebellar ataxia.

Spinocerebellar ataxia (SCA) is a heterogeneous genetic disorder with overlapping clinical phenotypes arising from the degeneration of purkinje cells and other regions of the brain. There are approximately 36 different subtypes of SCA, but SCA 1, 2, 3, 6 and 7 are most prevalent in the Indian population. Many findings suggested that cerebellar Purkinje cells region may be a uniquely vulnerable neuronal cell type, and more susceptible to a wider variety of genetic or cellular problems than other neuron types. In this review we emphasized mainly five common subtypes of SCA (1, 2, 3, 6 and 7) their pathophysiology, therapeutics, drugs studies and the technical challenges in the field of molecular genetic diagnosis.