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oculopharyngeal muscular dystrophy
Pathology:
- intranuclear filamentous inclusions or aggregates are detected in the myocytes of patients; these inclusions contain PABPN1, ubiquitin, subunits of the proteasome & poly(A) RNA
- the association of the expanded polyalanine mutations together with the capability to oligomerize may induce these inclusions & cell death
- expanded polyalanine mutations may either result from unequal crossing over during germ cell homologous recombination or from DNA slippage
- the pathogenic mechanisms mediated by polyalanine expansion mutations may be either a general disruption of cellular RNA metabolism due to the trapping by the inclusions of PABPN1, mRNAs &/or nuclear proteins, resulting in the induction of cell death; or may change normal muscle cell differentiation
Genetics:
1) autosomal dominant & autosomal recessive forms
2) defects in polyadenylate-binding protein 2 (PABPN1)
3) locus near region of cardiac alpha & beta myosin heavy chain genes
Clinical manifestations:
- late-onset slowly progressive myopathy characterized by
a) eyelid ptosis
b) dysphagia
c) cranial muscle weakness & proximal limb weakness (sometimes)
General
muscular dystrophy
polyalanine expansion disorder
Database Correlations
OMIM correlations
MORBIDMAP 602279
References
- Brais B et al
The oculopharyngeal muscular dystrophy locus maps to the
region of the cardiac alpha and beta myosin heavy chain genes
on chromosome 14q11.2-q13.
Hum Mol Genetics 4:429-34 1995
PMID: 7795598
- Brown LY & Brown SA.
Alanine tracts: the expanding story of human illness and
trinucleotide repeats.
Trends in Genetics 20(1):51-58, 2004
PMID: 14698619