The spectrum of GNE mutations: allelic heterogeneity for a common phenotype

• Published in: Neurological sciences Vol. 31; no. 3; pp. 377 - 380
• Main Authors: Grandis, Marina, Gulli, Rossella, Cassandrini, Denise, Gazzerro, Elisabetta, Benedetti, Luana, Narciso, Eleonora, Nobbio, Lucilla, Bruno, Claudio, Minetti, Carlo, Bellone, Emilia, Reni, Lizia, Mancardi, Giovanni Luigi, Mandich, Paola, Schenone, Angelo
• Format: Journal Article
• Language: English
• Published: Milan Springer Milan 01-06-2010; Springer Nature B.V
• Subjects: Adult; Alleles; Case Report; Disease Progression; Egypt; Female; Humans; Islam; Italy; Male; Medicine; Medicine & Public Health; Multienzyme Complexes - genetics; Muscle, Skeletal - pathology; Mutation, Missense; Myositis, Inclusion Body - genetics; Myositis, Inclusion Body - pathology; Neurology; Neuroradiology; Neurosciences; Neurosurgery; Phenotype; Psychiatry; Young Adult; Italy; Egypt; UDP; Hereditary inclusion body myopathy (IBM2); Rimmed vacuoles; Distal myopathy with rimmed vacuoles (DMRV); Middle Eastern Jewish founder mutation; acetylmannosamine kinase (GNE); Nonaka myopathy; Acetylglucosamine 2-epimerase
• ISSN: 1590-1874; 1590-3478
• DOI: 10.1007/s10072-010-0248-y

Hereditary inclusion body myopathy (IBM2) was mainly reported in Middle Eastern Jewish patients. Distal myopathy with rimmed vacuoles has been described as a worldwide distributed distal myopathy. Both diseases are caused by mutations of the UDP-
N
-acetylglucosamine 2-epimerase/
N
-acetylmannosamine kinase (
GNE
) gene. Herein we report two patients: an Egyptian Muslim patient with the “common” Middle Eastern mutation (M712T), rarely described in non-Jewish patients; and an Italian patient carrying a novel
GNE
mutation (L179F) in the epimerase domain. Our patients share common clinical and histopathological features, with some interesting aspects. The first patient presented a clinical deterioration during her first pregnancy confirming that an increased requirement of sialic acid during pregnancy may trigger a clinical worsening. The second patient showed a slowly progressive deterioration, different from other patients carrying mutations in the epimerase domain, who had a severe and rapid progression.