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Mobility shift of beta-dystroglycan as a marker of GMPPB gene-related muscular dystrophy

Lookup NU author(s): Dr Marta Bertoli, Dr Chiara Marini Bettolo, Professor Hanns Lochmuller, Professor Volker StraubORCiD, Emerita Professor Katherine Bushby, Dr Rita Barresi


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© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. Background: Defects in glycosylation of alphadystroglycan (α-DG) cause autosomal-recessive disorders with wide clinical and genetic heterogeneity, with phenotypes ranging from congenital muscular dystrophies to milder limb girdle muscular dystrophies. Patients show variable reduction of immunoreactivity to antibodies specific for glycoepitopes of α-DG on a muscle biopsy. Recessive mutations in 18 genes, including guanosine diphosphate mannose pyrophosphorylase B (GMPPB), have been reported to date. With no specific clinical and pathological handles, diagnosis requires parallel or sequential analysis of all known genes. Methods: We describe clinical, genetic and biochemical findings of 21 patients with GMPPB-associated dystroglycanopathy. Results: We report eight novel mutations and further expand current knowledge on clinical and muscle MRI features of this condition. In addition, we report a consistent shift in the mobility of beta-dystroglycan (β-DG) on Western blot analysis of all patients analysed by this mean. This was only observed in patients with GMPPB in our large dystroglycanopathy cohort. We further demonstrate that this mobility shift in patients with GMPPB was due to abnormal N-linked glycosylation of β-DG. Conclusions: Our data demonstrate that a change in β-DG electrophoretic mobility in patients with dystroglycanopathy is a distinctive marker of the molecular defect in GMPPB.

Publication metadata

Author(s): Sarkozy A, Torelli S, Mein R, Henderson M, Phadke R, Feng L, Sewry C, Ala P, Yau M, Bertoli M, Willis T, Hammans S, Manzur A, Sframeli M, Norwood F, Rakowicz W, Radunovic A, Vaidya SS, Parton M, Walker M, Marino S, Offiah C, Farrugia ME, Mamutse G, Marini-Bettolo C, Wraige E, Beeson D, Lochmuller H, Straub V, Bushby K, Barresi R, Muntoni F

Publication type: Article

Publication status: Published

Journal: Journal of Neurology, Neurosurgery and Psychiatry

Year: 2018

Volume: 89

Issue: 7

Pages: 762-768

Print publication date: 01/07/2018

Online publication date: 03/02/2018

Acceptance date: 03/01/2018

ISSN (print): 0022-3050

ISSN (electronic): 1468-330X

Publisher: BMJ Group


DOI: 10.1136/jnnp-2017-316956


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