This report describes facioscapulohumeral muscular dystrophy (FSHD), FRG1-related; FSHD exhibits autosomal dominant inheritance. Most cases of FSHD are associated with contraction of a D4Z4 repeat region on chromosome 4; FRG1 (FSHD region gene 1) maps close to this region. FRG1 is postulated to be transcriptionally regulated by the human DUX4 gene, a copy of which lies within each D4Z4 repeat unit (although only the distal copy may be functional). Contraction of the D4Z4 repeat region appears to result in epigenetic chromatin relaxation and overexpression of the DUX4 gene, resulting in misexpression of genes normally regulated by DUX4. There is a single gene orthologous to FRG1 in Drosophila, Dmel\FRG1, for which UAS and RNAi constructs are available. See also the human disease model report for FSHD, DUX4-related (FBhh0000650).
The human FRG1 gene has not been introduced into flies.
In flies, FRG1 is normally expressed at low to moderate levels in most assayed tissues and stages. Animals with muscle-specific or neural-specific reduction of expression effected by RNAi are viable. Overexpression of Dmel\FRG1 in adult muscle impairs flight and results in abnormalities of the thoracic musculature.
[updated Oct.2017 by FlyBase; FBrf0222196]
[FACIOSCAPULOHUMERAL MUSCULAR DYSTROPHY 1; FSHD1](https://omim.org/entry/158900)
[FACIOSCAPULOHUMERAL MUSCULAR DYSTROPHY 1; FSHD1](https://omim.org/entry/158900)
Facioscapulohumeral muscular dystrophy (FSHD) typically presents before age 20 years with weakness of the facial muscles and the stabilizers of the scapula or the dorsiflexors of the foot. Weakness is slowly progressive and severity is highly variable; approximately 20% of affected individuals eventually require a wheelchair. Life expectancy is not shortened. [Gene Reviews, Facioscapulohumeral Muscular Dystrophy (Lemmers, et al., 2014)]
Facioscapulohumeral muscular dystrophy is the third most common hereditary disease of muscle after Duchenne (DMD) and myotonic dystrophy. It is a highly variable disorder with weakness appearing from infancy to late life but typically in the second decade. In general, the disease initially involves the face and the scapulae followed by the foot dorsiflexors and the hip girdles, with striking asymmetry of muscle involvement from side to side (Tawil et al., 1998; pubmed:9506542). [from MIM:158900; 2017.10.31]
FSHD exhibits autosomal dominant inheritance. [Gene Cards, DUX4; 2017.10.31]
Facioscapulohumeral muscular dystrophy-1 (FSHD1) is associated with contraction of the D4Z4 macrosatellite repeat in the subtelomeric region of chromosome 4q35. [from MIM:158900; 2017.10.31]
DUX4 encodes a transcription factor expressed in multiple tissues including testis and pluripotent stem cells; in FSHD, increased levels of DUX4 lead to aberrant regulation of target genes. FRG1 is postulated to be such an affected target gene (FBrf0231179 and references cited therein).
Gabellini et al. (2002; pubmed:12176321) found that in FSHD muscle, genes located upstream of the D4Z4 macrosatellite repeat, including FRG1, FRG2, and ANT1, are inappropriately overexpressed. [from MIM:601278; 2017.10.31]
One to one (1 human to 1 Drosophila).
High-scoring ortholog of human FRG1 (1 Drosophila to 1 human); Dmel\FRG1 shares 48% identity and 64% similarity with the human gene.
