GNE myopathy in Roma patients homozygous for the p.I618T founder mutation.

Abstract

GNE myopathy is an autosomal-recessive disorder caused by mutations in the GNE gene, encoding the key enzyme in the sialic acid biosynthetic pathway, UDP-N-acetylglucosamine 2-epimerase/N-acetyl mannosamine kinase. We studied 50 Bulgarian Roma patients homozygous for p.I618T, an ancient founder mutation in the kinase domain of the GNE gene, dating before the Gypsy exodus from North West India. The clinical features in the Bulgarian GNE group can be described with disease onset mostly in the third decade, but in individual cases, onset was as early as 10 years of age. The majority of patients had foot drop as the first symptom, but three patients developed hand weakness first. Muscle weakness was early and severe for the tibialis anterior, and minimal or late for quadriceps femoris, and respiratory muscles were only subclinically affected even in the advanced stages of the disease. During a 15-year follow-up period, 32 patients became non-ambulant. The average period between disease onset and loss of ambulation was 10.34 ± 4.31 years, ranging from 3 to 20 years. Our analysis of affected sib pairs suggested a possible role of genetic modifying factors, accounting for significant variation in disease severity.

• Authors: Teodora Chamova, Velina Guergueltcheva, Mariana Gospodinova, Sabine Krause, Sebahattin Cirak, Ara Kaprelyan, Lyudmila Angelova, Violeta Mihaylova, Stoyan Bichev, David Chandler, Emanuil Naydenov, Margarita Grudkova, Presian Djukmedzhiev, Thomas Voit, Oksana Pogoryelova, Hanns Lochmüller, Hans H Goebel, Melanie Bahlo, Luba Kalaydjieva, Ivailo Tournev
• Journal: Neuromuscular disorders : NMD (Neuromuscul Disord) Vol. 25 Issue 9 Pg. 713-8 (Sep 2015) ISSN: 1873-2364 [Electronic] England
• PMID: 26231298 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 Elsevier B.V. All rights reserved.

Chemical References

• Multienzyme Complexes
• UDP-N-acetylglucosamine 2-epimerase - N-acetylmannosamine kinase

Topics

• Adolescent
• Adult
• Child
• Disease Progression
• Distal Myopathies (complications, ethnology, genetics, physiopathology)
• Female
• Follow-Up Studies
• Founder Effect
• Homozygote
• Humans
• Male
• Multienzyme Complexes (genetics)
• Mutation
• Pedigree
• Roma
• Young Adult