Novel FHL1 mutation in a family with reducing body myopathy

Abstract

In this study we highlighted diagnostic clues in this myopathy and compared our data with the literature.

FHL1 mutations that cause clinically distinct human myopathies form protein aggregates and impair myoblast differentiation

“…FHL1 protein is expressed at reduced, normal or elevated levels in RBM patient muscle Shalaby et al, 2009;Schreckenbach et al, 2013) (supplementary material Table S1). By contrast, SPM muscle exhibits absent, reduced or normal levels of FHL1 protein expression (Quinzii et al, 2008), and FHL1 is absent from XMPMA-afflicted muscle, as assessed by FHL1 immunoblot analysis (Windpassinger et al, 2008;Schoser et al, 2009).…”

“…Benign cases of RBM have a very low prevalence of reducing bodies, between 0.2 and 0.5% of biopsied muscle fibres (Tomé and Fardeau, 1975;Oh et al, 1983), and inclusion prevalence varies between muscle fascicles (Schreckenbach et al, 2013). It is interesting to speculate that SPM and XMPMA might represent a continuum of benign RBM with a low abundance of reducing bodies that are difficult to detect or are cleared in affected muscle biopsies.…”

“…FHL1 is mutated in six clinically distinct human myopathies, including reducing body myopathy (RBM) Schessl et al, 2009;Shalaby et al, 2009;Schessl et al, 2010;Selcen et al, 2011;Schreckenbach et al, 2013), X-linked dominant scapuloperoneal myopathy (SPM) (Quinzii et al, 2008;Chen et al, 2010), X-linked myopathy with postural muscle atrophy (XMPMA) (Windpassinger et al, 2008), rigidspine syndrome (RSS) (Shalaby et al, 2008), hypertrophic cardiomyopathy (HCM) (Friedrich et al, 2012) and EmeryDreifuss muscular dystrophy (EDMD) (Gueneau et al, 2009;Knoblauch et al, 2010). In RBM, both missense and deletion mutations affecting cysteine and histidine residues in FHL1 LIM domain-2 have been reported (see Fig.…”

Aggresome–Autophagy Involvement in a Sarcopenic Patient with Rigid Spine Syndrome and a p.C150R Mutation in FHL1 Gene

“…The diseases described so far include X-linked myopathy with postural muscle atrophy (XMPMA) (Windpassinger et al, 2008), reducing body myopathy (RBM) (Schessl et al, 2009; Shalaby et al, 2009; Selcen et al, 2011; Schreckenbach et al, 2013), X-linked dominant scapuloperoneal myopathy (Quinzii et al, 2008; Chen et al, 2010), rigid spine syndrome (RSS) (Shalaby et al, 2008), hypertrophic cardiomyopathy (Friedrich et al, 2012), and Emery–Dreifuss muscular dystrophy (Gueneau et al, 2009; Knoblauch et al, 2010). RBM is characterized by the presence of intracellular protein aggregates called “reducing bodies (RBs)” mainly containing mutated FHL1 protein, cytoskeletal and intermediate filament proteins, and components of the unfolded protein response pathway (Liewluck et al, 2007).…”

Adverse clinical course and poor prognosis of hypertrophic cardiomyopathy due to mutations in FHL1

“…FHL1 plays an important role in sarcomeric protein synthesis, maintenance of cellular integrity, intracellular signaling and genetic transcription [1]. Diseases related to FHL1 mutations comprise X-linked skeletal myopathies and also diverse cardiomyopathies as part of these syndromes (Table 2) [2][3][4]. Non-syndromic cardiac involvement has been recently described [5,6].…”