Sudha Bhattacharya1,2, Satish V Khadilkar3, Atchayaram Nalini4, Aparna Ganapathy5, Ashraf U Mannan5, Partha P Majumder6, Alok Bhattacharya7,2. 1. School of Environmental Sciences, Jawaharlal Nehru University, New Delhi, India. 2. World Without GNE Myopathy (India), New Delhi, India. 3. Department of Neurology, Grant Government Medical College and J.J. Hospital, Byculla, Mumbai, Maharashtra, India. 4. Departments of Neurology and Neuropathology, National Institute of Mental Health and Neurosciences, Bangalore, Karnataka, India. 5. Strand Life Sciences, Hebbal, Bangalore, India. 6. National Institute of Biomedical Genomics, Kalyani, West Bengal, India. 7. School of Life Sciences, Jawaharlal Nehru University, New Delhi, India.
Abstract
BACKGROUND: GNE myopathy is an adult onset recessive genetic disorder that affects distal muscles sparing the quadriceps. GNE gene mutations have been identified in GNE myopathy patients all over the world. Homozygosity is a common feature in GNE myopathy patients worldwide. OBJECTIVES: The major objective of this study was to investigate the mutation spectrum of GNE myopathy in India in relation to the population diversity in the country. MATERIALS AND METHODS: We have collated GNE mutation data of Indian GNE myopathy patients from published literature and from recently identified patients. We also used data of people of Indian subcontinent from 1000 genomes database, South Asian Genome database and Strand Life Science database to determine frequency of GNE mutations in the general population. RESULTS: A total of 67 GNE myopathy patients were studied, of whom 21% were homozygous for GNE variants, while the rest were compound heterozygous. Thirty-five different mutations in the GNE gene were recorded, of which 5 have not been reported earlier. The most frequent mutation was p.Val727Met (65%) found mainly in the heterozygous form. Another mutation, p.Ile618Thr was also common (16%) but was found mainly in patients from Rajasthan, while p.Val727Met was more widely distributed. The latter was also seen at a high frequency in general population of Indian subcontinent in all the databases. It was also present in Thailand but was absent in general population elsewhere in the world. CONCLUSION: p.Val727Met is likely to be a founder mutation of Indian subcontinent.
BACKGROUND:GNEmyopathy is an adult onset recessive genetic disorder that affects distal muscles sparing the quadriceps. GNE gene mutations have been identified in GNEmyopathypatients all over the world. Homozygosity is a common feature in GNEmyopathypatients worldwide. OBJECTIVES: The major objective of this study was to investigate the mutation spectrum of GNEmyopathy in India in relation to the population diversity in the country. MATERIALS AND METHODS: We have collated GNE mutation data of Indian GNEmyopathypatients from published literature and from recently identified patients. We also used data of people of Indian subcontinent from 1000 genomes database, South Asian Genome database and Strand Life Science database to determine frequency of GNE mutations in the general population. RESULTS: A total of 67 GNEmyopathypatients were studied, of whom 21% were homozygous for GNE variants, while the rest were compound heterozygous. Thirty-five different mutations in the GNE gene were recorded, of which 5 have not been reported earlier. The most frequent mutation was p.Val727Met (65%) found mainly in the heterozygous form. Another mutation, p.Ile618Thr was also common (16%) but was found mainly in patients from Rajasthan, while p.Val727Met was more widely distributed. The latter was also seen at a high frequency in general population of Indian subcontinent in all the databases. It was also present in Thailand but was absent in general population elsewhere in the world. CONCLUSION:p.Val727Met is likely to be a founder mutation of Indian subcontinent.
Entities:
Keywords:
GNE myopathy; Indian subcontinent; founder mutation; mutations
Authors: Marco Savarese; Jaakko Sarparanta; Anna Vihola; Per Harald Jonson; Mridul Johari; Salla Rusanen; Peter Hackman; Bjarne Udd Journal: Acta Myol Date: 2020-12-01