This report describes reducing body myopathy 1A (RBM, RBM1A), one of multiple myopathies associated with the human gene FHL1 (see MIM:300163). FHL1 (Four And A Half LIM Domains 1) is involved in muscle growth and differentiation, sarcomere assembly, and in regulation of transcription factors. There is no gene closely related to FHL1 in Drosophila.
Multiple UAS constructs of the human Hsap\FHL1 gene have been introduced into flies, including wild-type and a variant (C150Y) implicated in human disease. Expression of the variant form in muscle results in reduced flight ability; in the adult indirect flight muscles sarcomeric defects and accumulation of protein aggregates similar to the human disease phenotype are observed. See the 'Disease-implicated Variants' table, below.
[updated Dec. 2021 by FlyBase; FBrf0222196]
[REDUCING BODY MYOPATHY, X-LINKED 1A, SEVERE, WITH INFANTILE OR EARLY CHILDHOOD ONSET; RBMX1A](https://omim.org/entry/300717)
[FOUR-AND-A-HALF LIM DOMAINS 1; FHL1](https://omim.org/entry/300163)
Reducing body myopathy (RBM) is a rare disease marked by progressive muscle weakness caused by a mutation in the FHL1 gene. Reported cases can be separated into two groups: cases with mean age onset 7.6 +/- 5 years and cases with mean age onset 26.7 +/- 4.2 years. The initial symptoms, rigid spine, contractures, scoliosis and axial and neck weaknesses, dysphagia, cardiac involvement, are predominant in the younger group. (Mota et al., 2021; pubmed:34366191)
Mutations of the FHL1 gene are implicated in multiple X-linked myopathies. Clinical phenotype varies between and within each entity, with varying degrees of progression. The involvement of spinal and scapuloperoneal muscles is common to all. Histologically, reducing bodies (RBs) are seen in all phenotypes except EDMD (FBrf0251822 and references cited therein).
Reducing-body myopathy (RBM) is a rare myopathy characterized pathologically by the presence of intracytoplasmic inclusion bodies strongly stained by menadione-linked alpha-glycerophosphate dehydrogenase (MAG). The clinical features of RBM are variable; a severe form has onset in infancy or early childhood and results in severe disability or early death, and a less severe form has onset in late childhood or adulthood. [from MIM:300717; 2021.11.30]
Both severe and less severe forms of RBM are caused by mutation in the FHL1 gene.
[from MIM:300717; 2021.11.30]
The term 'reducing body' refers to the reducing activity of the inclusions to nitroblue tetrazolium (NBT) in the absence of substrate. This condition is also commonly associated with rimmed vacuoles and cytoplasmic bodies. [from MIM:300717; 2021.11.30]
FHL1 (Four And A Half LIM Domains 1) is involved in muscle growth and differentiation, sarcomere assembly, and in regulation of transcription factors; it is expressed in cardiac and striated muscle (FBrf0251822 and references cited therein).
There is no gene closely related to FHL1 in Drosophila.
