Biología celular: investigación y terapia

Molecular Spectrum, Family Screening And Genetic Counselling Of Spinocerebellar Ataxia (SCA) Cases In An Indian Scenario

Priyanka Vishwakarma

Spinocerebellar Ataxia (SCA) is an adult-onset autosomal dominant disorder and childhood onset also reported. It is heterogeneous in nature and mainly caused by a triplet repeat expansion and sometimes repeats can be pentanucleotide and hexanucleotide, however SCA can also be caused by point or missense mutations. Till date, the clinical diagnosis of SCA is primarily based on the phenotypic features like ataxia, nystagmus, dysphagia, dysmetria etc followed by confirmation through molecular diagnosis. To characterize the status of repeat ranges in Spinocerebellar ataxia in Indian cases and provide the extended family screening. The present study was conducted with 70 clinically suspected SCA cases. For the molecular diagnosis, Multiplex PCR (M-PCR) was used for SCA subtypes1, 2, 3, 6, 7, 10, 12 and 17 that are the common subtypes in Indian population. TP-PCR was further used in case of SCA2, 7 and 10 for identification of large pathogenic expansions. Extended family screening and genetic counselling was offered to all the positive cases identified. Out of the enrolled 70 SCA suspects, overall 18 (25%) were found to be positive for various SCA subtypes by molecular analysis. These 18 SCA confirmed cases included 5 SCA1 subtype (28%) , 6 SAC2 subtype (34%), 2 SCA3 subtype (12%), 3 SCA7 subtype (16%) and one each for SCA6 (1%) and SCA17 (1%) subypes. Genetic counselling and extended family screening was offered to all the 18 positive SCA cases and yielded additional nine cases. The present study established that M-PCR followed by TP-PCR (in case of SCA2, 7 and 10) could be successfully used for the detection of CAG repeat expansion in SCA suspects and for confirmation of their respective subtypes, owing to its reliability, rapidity and cost-effectiveness.