A recurrent GNE variant causing GNE myopathy in unrelated patients from Pakistan: a case series

Abstract Background GNE myopathy, also referred to as bifunctional UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase myopathy, is a progressive distal myopathy marked by rimmed vacuoles and linked to a variety of disease-causing genetic variants. These variants display considerable ethnic diversity worldwide. However, no studies to date have explored GNE disease variants in the Pakistani population. Case presentation We report four unrelated adolescent male patients, from Pakistan, diagnosed with GNE myopathy. All four patients shared variant, c.2179G > A (p. Val727Met), which has previously been observed in Indian populations. Among these patients, three exhibited the variant in a compound heterozygous state along with a second variant; three out of four patients were born to consanguineous parents with positive family history of similar weakness in all cases described. Symptoms in these patients began at an average age of 21.5 years; three of the four patients became wheelchair dependent within 10 years from symptoms onset. Conclusion The GNE variant c.2179G > A (p. Val727Met) is not exclusive to the Indian Rajasthani population but could also be prevalent in Pakistan, likely owing to shared South Asian ancestry. This report represents the first case series from Pakistan focusing on a specific GNE variant, providing a valuable addition to the genetic understanding of GNE myopathy in this population. This finding underscores the need for further genetic studies to explore the presence and impact of GNE variants in Pakistan and neighboring South Asian regions.