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Clinical utility of RNA sequencing to resolve unusual GNE myopathy with a novel promoter deletion
Author(s) -
Chakravorty Samya,
Berger Kiera,
Arafat Dalia,
Nallamilli Babi Ramesh Reddy,
Subramanian Hari Prasanna,
Joseph Soumya,
Anderson Mary E.,
Campbell Kevin P.,
Glass Jonathan,
Gibson Greg,
Hegde Madhuri
Publication year - 2019
Publication title -
muscle and nerve
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.025
H-Index - 145
eISSN - 1097-4598
pISSN - 0148-639X
DOI - 10.1002/mus.26486
Subject(s) - myopathy , genetics , biology , phenotype , gene , transcriptome , computational biology , gene expression
: UDP N‐acetylglucosamine2‐epimerase/N‐acetylmannosamine‐kinase ( GNE ) gene mutations can cause mostly autosomal‐recessive myopathy with juvenile‐onset known as hereditary inclusion‐body myopathy (HIBM). Methods : We describe a family of a patient showing an unusual HIBM with both vacuolar myopathy and myositis without quadriceps‐sparing, hindering diagnosis. We show how genetic testing with functional assays, clinical transcriptome sequencing (RNA‐seq) in particular, helped facilitate both the diagnosis and a better understanding of the genotype‐phenotype relationship. Results : We identified a novel 7.08 kb pathogenic deletion upstream of GNE using array comparative genomic hybridization (aCGH) and a common Val727Met variant. Using RNA‐seq, we found only monoallelic (Val727Met‐allele) expression, leading to ~50% GNE reduction in muscle. Importantly, α‐dystroglycan is hypoglycosylated in the patient muscle, suggesting HIBM could be a “dystroglycanopathy.” Conclusions : Our study shows the importance of considering aCGH for GNE‐myopathies, and the potential of RNA‐seq for faster, definitive molecular diagnosis of unusual myopathies. Muscle Nerve , 2019