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J Neuromuscul Dis. 2015 Jun 4;2(2):131-136.

Novel Pathogenic Variants in a French Cohort Widen the Mutational Spectrum of GNE Myopathy.

Author information

1
Aix Marseille Université, INSERM, GMGF UMR_S 910, 13385, Marseille, France.
2
APHM, Département de Génétique Médicale, Hôpital Timone Enfants, 13385, Marseille, France.
3
Institut de Myologie, APHP, Groupe Hospitalier La Pitié Salpêtrière, 75013, Paris, France.
4
APHP, Hôpital Marin, 64700, Hendaye, France.

Abstract

BACKGROUND:

GNE myopathy is a rare autosomal recessively inherited muscle disease resulting from mutations in the gene encoding GNE (UDP-N-acetylglucosamine-2-epimerase/N-acetylmannosamine kinase), a key enzyme in sialic acid biosynthesis. 154 different pathogenic variants have been previously associated with GNE myopathy.

OBJECTIVE:

Describe novel pathogenic variants associated with GNE myopathy in a large French cohort.

METHODS:

We analyzed mutational data from 32 GNE myopathy index patients. Novel, as well as previously published pathogenic variants, were examined for possible deleterious effects on splicing.

RESULTS:

We describe 13 novel pathogenic variants in GNE, identified in the first large French cohort reported to date. We also find that 6 published pathogenic variants might have a previously unrecognized deleterious effect on splicing.

CONCLUSIONS:

Novel pathogenic GNE variants described here raise the total number of different pathogenic variants reported to 167, complementing the recently published GNE mutation update. Our novel findings on possible splice-disrupting effects by several variants suggest that the pathogenicity mechanism of these variants could be reinterpreted, expanding our knowledge about the GNE mutational spectrum.

KEYWORDS:

Distal myopathy with rimmed vacuoles; GNE; mutation; nonaka; splicing

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