Bugiardini, E;
Khan, A;
Phadke, R;
Lynch, DS;
Cortese, A;
Feng, L;
Gang, Q;
... Hanna, MG; + view all
(2019)
Genetic and phenotypic characterisation of inherited myopathies in a tertiary neuromuscular centre.
Neuromuscular Disorders
, 29
(10)
pp. 747-757.
10.1016/j.nmd.2019.08.003.
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Abstract
Diagnosis of inherited myopathies can be a challenging and lengthy process due to broad genetic and phenotypic heterogeneity. In this study we applied focused exome sequencing to investigate a cohort of 100 complex adult myopathy cases who remained undiagnosed despite extensive investigation. We evaluated the frequency of genetic diagnoses, clinical and pathological factors most likely to be associated with a positive diagnosis, clinical pitfalls and new phenotypic insights that could help to guide future clinical practice. We identified pathogenic/likely pathogenic variants in 32/100 cases. TTN-related myopathy was the most common diagnosis (4/32 cases) but the majority of positive diagnoses related to a single gene each. Childhood onset of symptoms was more likely to be associated with a positive diagnosis. Atypical and new clinico-pathological phenotypes with diagnostic pitfalls were identified. These include the new emerging group of neuromyopathy genes (HSPB1, BICD2) and atypical biopsy findings: COL6A-related myopathy with mitochondrial features, DOK7 presenting as myopathy with minicores and DES-related myopathy without myofibrillar pathology. Our data demonstrates the diagnostic efficacy of broad NGS screening when combined with detailed clinico-pathological phenotyping in a complex neuromuscular cohort. Atypical clinico-pathological features may delay the diagnostic process if smaller targeted gene panels are used.
| Type: | Article |
|---|---|
| Title: | Genetic and phenotypic characterisation of inherited myopathies in a tertiary neuromuscular centre |
| Location: | Snowbird, UT |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1016/j.nmd.2019.08.003 |
| Publisher version: | https://doi.org/10.1016/j.nmd.2019.08.003 |
| Language: | English |
| Additional information: | This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions. |
| Keywords: | Science & Technology, Life Sciences & Biomedicine, Clinical Neurology, Neurosciences, Neurosciences & Neurology |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Department of Neuromuscular Diseases |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10084679 |
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