title: Muscle hypertrophy as the presenting sign in a patient with a complete FHL1 deletion.
abstract: Four and a half LIM protein 1 (FHL1/SLIM1) has recently been identified as the causative gene mutated in four distinct diseases affecting skeletal muscle that have overlapping features, including reducing body myopathy, X-linked myopathy, X-linked dominant scapuloperoneal myopathy and Emery-Dreifuss muscular dystrophy. FHL1 localises to the sarcomere and the sarcolemma and is believed to participate in muscle growth and differentiation as well as in sarcomere assembly. We describe in this case report a boy with a deletion of the entire FHL1 gene who is now 15 years of age and presented with muscle hypertrophy, reduced subcutaneous fat, rigid spine and short stature. This case is the first, to our knowledge, with a complete loss of the FHL1 protein and MAP7D3 in combination. It supports the theory that dominant negative effects (accumulation of cytotoxic-mutated FHL1 protein) worsen the pathogenesis. It extends the phenotype of FHL1-related myopathies and should prompt future testing in undiagnosed patients who present with unexplained muscle hypertrophy, contractures and rigid spine, particularly if male.
authors.affiliation: John Walton Muscular Dystrophy Research Centre, Institute of Genetic Medicine, Newcastle upon Tyne, UK.
authors.forename: T A
authors.initials: TA
authors.lastname: Willis
authors.affiliation: John Walton Muscular Dystrophy Research Centre, Institute of Genetic Medicine, Newcastle upon Tyne, UK.
authors.forename: C L
authors.identifier: http://orcid.org/0000-0002-6084-5174
authors.initials: CL
authors.lastname: Wood
authors.affiliation: John Walton Muscular Dystrophy Research Centre, Institute of Genetic Medicine, Newcastle upon Tyne, UK.
authors.forename: J
authors.initials: J
authors.lastname: Hudson
authors.affiliation: Institute of Neuroscience, Newcastle University, Newcastle upon Tyne, UK.
authors.forename: T
authors.initials: T
authors.lastname: Polvikoski
authors.affiliation: John Walton Muscular Dystrophy Research Centre, Institute of Genetic Medicine, Newcastle upon Tyne, UK.|Rare Diseases Advisory Group Service for Neuromuscular Diseases, Muscle Immunoanalysis Unit, Newcastle upon Tyne, UK.
authors.forename: R
authors.initials: R
authors.lastname: Barresi
authors.affiliation: John Walton Muscular Dystrophy Research Centre, Institute of Genetic Medicine, Newcastle upon Tyne, UK.
authors.forename: H
authors.initials: H
authors.lastname: Lochmüller
authors.affiliation: John Walton Muscular Dystrophy Research Centre, Institute of Genetic Medicine, Newcastle upon Tyne, UK.
authors.forename: K
authors.initials: K
authors.lastname: Bushby
authors.affiliation: John Walton Muscular Dystrophy Research Centre, Institute of Genetic Medicine, Newcastle upon Tyne, UK.
authors.forename: V
authors.initials: V
authors.lastname: Straub
mesh_terms: D000293:Adolescent; D017353:Gene Deletion; D015870:Gene Expression; D006801:Humans; D006984:Hypertrophy / Q000235:genetics* / Q000473:pathology; D047908:Intracellular Signaling Peptides and Proteins / Q000172:deficiency / Q000235:genetics*; D060588:LIM Domain Proteins / Q000172:deficiency / Q000235:genetics*; D008297:Male; D008869:Microtubule-Associated Proteins / Q000172:deficiency / Q000235:genetics*; D009124:Muscle Proteins / Q000172:deficiency / Q000235:genetics*; D009135:Muscular Diseases / Q000235:genetics* / Q000473:pathology; D010641:Phenotype; D013131:Spine / Q000378:metabolism / Q000473:pathology*; D050151:Subcutaneous Fat / Q000378:metabolism / Q000473:pathology*
chemical_list: C101149:FHL1 protein, human; D047908:Intracellular Signaling Peptides and Proteins; D060588:LIM Domain Proteins; C574933:MAP7D3 protein, human; D008869:Microtubule-Associated Proteins; D009124:Muscle Proteins
keywords: Emery–Dreifuss; FHL1; muscular dystrophy; neuromuscular