Journal article
FXR1-related congenital myopathy: expansion of the clinical and genetic spectrum
Journal of medical genetics, Vol.59(11), pp.1069-1074
04/07/2022
DOI: 10.1136/jmedgenet-2021-108341
PMCID: PMC9537361
PMID: 35393337
Abstract
BackgroundBiallelic pathogenic variants in FXR1 have recently been associated with two congenital myopathy phenotypes: a severe form associated with hypotonia, long bone fractures, respiratory insufficiency and infantile death, and a milder form characterised by proximal muscle weakness with survival into adulthood.ObjectiveWe report eight patients from four unrelated families with biallelic pathogenic variants in exon 15 of FXR1.MethodsWhole exome sequencing was used to detect variants in FXR1.ResultsCommon clinical features were noted for all patients, which included proximal myopathy, normal serum creatine kinase levels and diffuse muscle atrophy with relative preservation of the quadriceps femoris muscle on muscle imaging. Additionally, some patients with FXR1-related myopathy had respiratory involvement and required bilevel positive airway pressure support. Muscle biopsy showed multi-minicores and type I fibre predominance with internalised nuclei.Conclusion FXR1-related congenital myopathy is an emerging entity that is clinically recognisable. Phenotypic variability associated with variants in FXR1 can result from differences in variant location and type and is also observed between patients homozygous for the same variant, rendering specific genotype–phenotype correlations difficult. Our work broadens the phenotypic spectrum of FXR1-related congenital myopathy.
Details
- Title: Subtitle
- FXR1-related congenital myopathy: expansion of the clinical and genetic spectrum
- Creators
- Magdalena Mroczek - University Hospital of ZurichCheryl Longman - Queen Elizabeth University HospitalMaria Elena Farrugia - Queen Elizabeth University HospitalSolange Kapetanovic Garcia - Unidad de ELA y Neuromuscular, Hospital Universitario de Basurto, Bilbao, SpainDidem Ardicli - Hacettepe University HospitalHaluk Topaloglu - Hacettepe University HospitalAurelio Hernández-Laín - Hospital Universitario 12 De OctubreDiclehan Orhan - Hacettepe UniversityMehmet Alikasifoglu - Hacettepe UniversityJennifer Duff - John Walton Muscular Dystrophy Research Centre, Translational and Clinical Research Institute, Newcastle University and Newcastle Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK.Sabine Specht - Newcastle UniversityKristen Nowak - Harry Perkins Institute of Medical ResearchGianina Ravenscroft - Harry Perkins Institute of Medical ResearchKatherine Chao - Broad InstituteZaheer Valivullah - Broad InstituteSandra Donkervoort - National Institute of Neurological Disorders and StrokeDimah Saade - National Institute of Neurological Disorders and StrokeCarsten Bönnemann - National Institute of Neurological Disorders and StrokeVolker Straub - John Walton Muscular Dystrophy Research Centre, Translational and Clinical Research Institute, Newcastle University and Newcastle Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK grace.yoon@utoronto.ca volker.straub@newcastle.ac.uk.Grace Yoon - University of Toronto
- Resource Type
- Journal article
- Publication Details
- Journal of medical genetics, Vol.59(11), pp.1069-1074
- DOI
- 10.1136/jmedgenet-2021-108341
- PMID
- 35393337
- PMCID
- PMC9537361
- NLM abbreviation
- J Med Genet
- ISSN
- 0022-2593
- eISSN
- 1468-6244
- Publisher
- BMJ Publishing Group Ltd
- Grant note
- APP1122952; APP2002640 / NHMRC R01 HG009141 / National Human Genome Research Institute (http://dx.doi.org/10.13039/100000051) Ultragenyx Pharmaceutical (http://dx.doi.org/10.13039/100013220) Limb Girdle Muscular Dystrophy 2i Research Fund (http://dx.doi.org/10.13039/100013780) National Institute of Neurological Disorders and Stroke (http://dx.doi.org/10.13039/100000065) Broad Institute of MIT and Harvard Center for Mendelian Genomics NIH Muscular Dystrophy UK (http://dx.doi.org/10.13039/501100008164) National Eye Institute (http://dx.doi.org/10.13039/100000053) Kurt+Peter Foundation (http://dx.doi.org/10.13039/100017992) Genzyme (http://dx.doi.org/10.13039/100004329) UM1 HG008900 / National Heart, Lung, and Blood Institute (http://dx.doi.org/10.13039/100000050) Samantha J. Brazzo Foundation, LGMD2D Foundation Coalition to Cure Calpain 3
- Language
- English
- Date published
- 04/07/2022
- Academic Unit
- Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Neurology (Pediatrics)
- Record Identifier
- 9984354119602771
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