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 from people of the Indian subcontinent from the 1000 Genomes database, the South Asian Genome database and the Strand Life Science database to determine the 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 the general population of the Indian subcontinent in all the databases. It was also present in Thailand but was absent in the general population elsewhere in the world.
Conclusion: p.Val727Met is likely to be a founder mutation of the Indian subcontinent.
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