Journal article
Clinical utility of RNA sequencing to resolve unusual GNE myopathy with a novel promoter deletion
Muscle & nerve, Vol.60(1), pp.98-103
07/2019
DOI: 10.1002/mus.26486
PMCID: PMC7688010
PMID: 30990900
Abstract
ABSTRACT\nIntroduction: 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
Details
- Title: Subtitle
- Clinical utility of RNA sequencing to resolve unusual GNE myopathy with a novel promoter deletion
- Creators
- Samya Chakravorty - Emory University School of MedicineKiera Berger - Georgia Institute of TechnologyDalia Arafat - Georgia Institute of TechnologyBabi Ramesh Reddy Nallamilli - Emory University School of MedicineHari Prasanna Subramanian - Georgia Institute of TechnologySoumya Joseph - University of Iowa Roy J. and Lucille A. Carver College of MedicineMary E Anderson - University of Iowa Roy J. and Lucille A. Carver College of MedicineKevin P Campbell - University of Iowa Roy J. and Lucille A. Carver College of MedicineJonathan Glass - Emory University School of MedicineGreg Gibson - Georgia Institute of TechnologyMadhuri Hegde - Perkin Elmer
- Resource Type
- Journal article
- Publication Details
- Muscle & nerve, Vol.60(1), pp.98-103
- DOI
- 10.1002/mus.26486
- PMID
- 30990900
- PMCID
- PMC7688010
- NLM abbreviation
- Muscle Nerve
- ISSN
- 0148-639X
- eISSN
- 1097-4598
- Publisher
- John Wiley & Sons, Inc; Hoboken, USA
- Number of pages
- 6
- Grant note
- Muscular Dystrophy Association (MDA418496; MDA578400)
- Language
- English
- Date published
- 07/2019
- Academic Unit
- Neurology; Molecular Physiology and Biophysics; Iowa Neuroscience Institute
- Record Identifier
- 9984068279302771
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