Oculopharyngeal muscle dystrophy

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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[1].

Mutations of PABPN1 cause oculopharyngeal muscle dystrophy. This seems to be through mitochondrial protein undersynthesis in those with the polyalanine triplet repeat expansion mutation[2]


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