Advanced Genetics (Jun 2022)

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

  • Pooja Sharma,
  • Akhilesh Kumar Sonakar,
  • Nishu Tyagi,
  • Varun Suroliya,
  • Manish Kumar,
  • Rintu Kutum,
  • Vivekananda Asokchandran,
  • Sakshi Ambawat,
  • Uzma Shamim,
  • Avni Anand,
  • Ishtaq Ahmad,
  • Sunil Shakya,
  • Bharathram Uppili,
  • Aradhana Mathur,
  • Shaista Parveen,
  • Shweta Jain,
  • Jyotsna Singh,
  • Malika Seth,
  • Sana Zahra,
  • Aditi Joshi,
  • Divya Goel,
  • Shweta Sahni,
  • Asangla Kamai,
  • Saruchi Wadhwa,
  • Aparna Murali,
  • Sheeba Saifi,
  • Debashish Chowdhury,
  • Sanjay Pandey,
  • Kuljeet Singh Anand,
  • Ranganathan Lakshmi Narasimhan,
  • Sanghamitra Laskar,
  • Suman Kushwaha,
  • Mukesh Kumar,
  • Cheruvallill Velayudhan Shaji,
  • Madakasira Vasantha Padma Srivastava,
  • Achal K. Srivastava,
  • Mohammed Faruq,
  • GOMED‐Ataxia study group

DOI
https://doi.org/10.1002/ggn2.202100078
Journal volume & issue
Vol. 3, no. 2
pp. n/a – n/a

Abstract

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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.

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