Two patients with GMPPB mutation: The overlapping phenotypes of limb-girdle myasthenic syndrome and limb-girdle muscular dystrophy dystroglycanopathy.

Abstract

INTRODUCTION:

Mutations in the guanosine diphosphate-mannose pyrophosphorylase-B gene (GMPPB) have been identified in congenital muscular dystrophies, limb-girdle muscular dystrophy (LGMD2T), and congenital myasthenic syndromes (CMSs); overall, 41 patients have been described.

METHODS:

Two patients presented with a myasthenic syndrome (patient 1; 74 years old) and rhabdomyolysis (patient 2; 23 years old). Examinations included repetitive nerve stimulation, muscle biopsy and whole-body MRI (WBMRI); next generation sequencing facilitated diagnosis.

RESULTS:

We identified the following GMPPB mutations: c.79G>C/c.859C>T in the 23-year-old man with LGMD2T-phenotype and c.79G>C homozygosity in the 74-year-old woman with CMS phenotype. WBMRI showed fatty degeneration of paraspinal, thigh adductor, and calf muscles in patient 1 and edematous changes of the soleus muscle in patient 2.

CONCLUSIONS:

This case of c.79G>C homozygosity causing a mild, late-onset CMS phenotype, confirms the mild nature of this common mutation. The descriptions of these 2 new GMPPB cases add to the knowledge regarding this recently discovered, heterogeneous disease. Muscle Nerve 56: 334-340, 2017.

• Authors: Federica Montagnese, Elisabeth Klupp, Dimitrios C Karampinos, Saskia Biskup, Dieter Gläser, Jan S Kirschke, Benedikt Schoser
• Journal: Muscle & nerve (Muscle Nerve) Vol. 56 Issue 2 Pg. 334-340 (08 2017) ISSN: 1097-4598 [Electronic] United States
• PMID: 27874200 (Publication Type: Case Reports, Research Support, Non-U.S. Gov't)
• Copyright: © 2016 Wiley Periodicals, Inc.

Chemical References

• Nucleotidyltransferases
• mannose 1-phosphate guanylyltransferase

Topics

• Aged
• Humans
• Muscular Dystrophies, Limb-Girdle (complications, genetics)
• Mutation (genetics)
• Myasthenic Syndromes, Congenital (genetics)
• Nucleotidyltransferases (genetics)
• Phenotype
• Young Adult