Oculopharyngeal muscle dystrophy
Oculopharyngeal muscle dystrophy (OPMD) is caused by the PABPN1 gene having a polyalanine triplet repeat expansion mutation. The wildtype (GCG)6 repeat encoding a polyalanine tract becomes a pathologic (GCG)8-13 repeat. This causes in late middle age the progressive degeneration muscles, leading to:
Inheritance is usually autosomial dominant. Cranial nerve and spincter involvement is known.
The PABPN1 gene at 14q11.2 codes for a 306 amino acid peptide polyadenylate-binding protein 2 which is a multifunctional regulator of mRNA processing. Three isoforms are produced by alternative splicing of this ubiquitous expressed gene. It facilitates the polyadenylation of messenger RNAs and poly(A) site selection. Poly(A) binding protein nuclear 1 levels are reduced in skeletal muscles from midlife onwards and so dysfunction of the gene seems associated with muscle ageing.
- ↑ Raz Y, Raz V. Oculopharyngeal muscular dystrophy as a paradigm for muscle aging. Frontiers in aging neuroscience. 2014; 6:317.(Epub) (Link to article – subscription may be required.)
- ↑ Chartier A, Klein P, Pierson S, Barbezier N, Gidaro T, Casas F, Carberry S, Dowling P, Maynadier L, Bellec M, Oloko M, Jardel C, Moritz B, Dickson G, Mouly V, Ohlendieck K, Butler-Browne G, Trollet C, Simonelig M. Mitochondrial dysfunction reveals the role of mRNA poly(A) tail regulation in oculopharyngeal muscular dystrophy pathogenesis. PLoS genetics. 2015 Mar; 11(3):e1005092.(Epub) (Link to article – subscription may be required.)