Genetics of Ataxias in Indian Population: A Collative Insight from a Common Genetic Screening Tool

Abstract

Cerebellar ataxias (CAs) represent a group of autosomal dominant and recessive neurodegenerative disorders affecting cerebellum with or without spinal cord. Overall, CAs have preponderance for tandem nucleotide repeat expansions as an etiological factor (10 TREs explain nearly 30–40% of ataxia cohort globally). The experience of 10 years of common genetic ataxia subtypes for ≈5600 patients’ referrals (Pan‐India) received at a single center is shared herein. Frequencies (in %, n) of SCA types and FRDA in the sample cohort are observed as follows: SCA12 (8.6%, 490); SCA2 (8.5%, 482); SCA1 (4.8%, 272); SCA3 (2%, 113); SCA7 (0.5%, 28); SCA6 (0.1%, 05); SCA17 (0.1%, 05), and FRDA (2.2%, 127). A significant amount of variability in TRE lengths at each locus is observed, we noted presence of biallelic expansion, co‐occurrence of SCA‐subtypes, and the presence of premutable normal alleles. The frequency of mutated GAA‐FRDA allele in healthy controls is 1/158 (0.63%), thus an expected FRDA prevalence of 1:100 000 persons. The data of this study are relevant not only for clinical decision making but also for guidance in direction of genetic investigations, transancestral comparison of genotypes, and lastly provide insight for policy decision for the consideration of SCAs under rare disease category.

Identification and the origin of GAA expansion in FGF14 (Spinocerebellar Ataxia Type 27B): an insight from Indian subcontinent suggests an ancient origin

“…However, this might be misleading when considering the overall uncharacterized ataxia cohort in which 1.83% accounts for this disorder.In the genetic spectrum of SCAs in the Indian population, SCA27B may emerge as a strong candidate locus asits frequency is 1.83% which is higher than the previously determined frequencies of SCA6 (0.1%), SCA 7 (0.5%), and SCA 17 (0.1%). Its frequency is close to that of SCA3 (2%) and FRDA (2.2%) which are well-established emerging ataxia disorders in India (10).…”

Genetic analysis of Indian sporadic young onset patient with Amyotrophic Lateral Sclerosis

“…The presence of pathogenic G4C2 hexanucleotide repeat expansions in C9orf72 was tested by Repeat-primed PCR assay along with fragment analysis [35] as well as trinucleotide CAG repeat sizes in ATXN -1 and ATXN -2 were also tested by PCR amplification by Fluorescently labelled primers [36] in the patient sample.…”

Molecular clues unveiling spinocerebellar ataxia type-12 pathogenesis

“… 3 Although most cases of SCA12 have been reported from the Indian subcontinent, a variety of rare presentations have been reported from different parts of the world. 4 …”