Clinical utility of RNA sequencing to resolve unusual GNE myopathy with a novel promoter deletion.
Muscle Nerve
; 60(1): 98-103, 2019 07.
Article
em En
| MEDLINE
| ID: mdl-30990900
ABSTRACT
INTRODUCTION:
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.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Regiões Promotoras Genéticas
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Miopatias Distais
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Complexos Multienzimáticos
Tipo de estudo:
Diagnostic_studies
/
Prognostic_studies
Limite:
Adult
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Humans
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Male
Idioma:
En
Revista:
Muscle Nerve
Ano de publicação:
2019
Tipo de documento:
Article