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MEGF10 related myopathies: A new case with adult onset disease with prominent respiratory failure and review of reported phenotypes

Lookup NU author(s): Dr Lizzie Harris, Dr Chiara Marini Bettolo, Dr Ana TopfORCiD, Dr Rita Barresi, Dr Tuomo Polvikoski, Dr Richard Charlton, Professor Michela GuglieriORCiD, Professor Hanns Lochmuller, Emerita Professor Katherine Bushby, Professor Volker StraubORCiD


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© 2017. Recessive mutations in MEGF10 (multiple epidermal growth factor 10) have been reported in a severe early onset disorder named Early Myopathy, Areflexia, Respiratory Distress and Dysphagia, and a milder form with cores in the muscle biopsy; and a possible genotype-phenotype correlation determining the clinical presentation has been suggested. We undertook exome sequencing in a 66 year old male with a 20 year history of progressive proximal and distal weakness of upper and lower limbs, facial weakness and dysphagia, who developed respiratory failure requiring ventilation while still ambulant in his 50s. Muscle biopsy demonstrated myopathic changes with aggregation of myofibrillar proteins. Mutations in MEGF10 were identified: a novel essential splice site (c.1426+1G>T) and a novel missense variant (c.352T>C, p.(Cys118Arg)). We performed a detailed review of all reported MEGF10 cases (n = 20), and confirmed the presence of a genotype-phenotype correlation, namely that with ≥1 null mutation onset of respiratory dysfunction occurs in the first year of life, whereas with 2 missense mutations, respiratory dysfunction occurs at 10 years old or much later, as in the patient reported here. Our findings expand the phenotype of MEGF10 mutations to include onset in the 5th decade, and discuss the spectrum of MEGF10 related disease.

Publication metadata

Author(s): Harris E, Marini-Bettolo C, Topf A, Barresi R, Polvikovski T, Bailey G, Charlton R, Tellez J, MacArthur D, Guglieri M, Lochmuller H, Bushby K, Straub V

Publication type: Article

Publication status: Published

Journal: Neuromuscular Disorders

Year: 2018

Volume: 28

Issue: 1

Pages: 48-53

Print publication date: 01/01/2018

Online publication date: 12/10/2017

Acceptance date: 28/09/2017

ISSN (print): 0960-8966

ISSN (electronic): 1873-2364

Publisher: Elsevier Ltd


DOI: 10.1016/j.nmd.2017.09.017


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