Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0026850 (muscular dystrophy)
 5,870 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The dominant oculo-pharyngeal muscular dystrophy mutation consists of an expanded (GCN)(12-17) in the coding region of the PolyA Binding Protein Nuclear 1 gene. A founder effect has been demonstrated in Canadian and Bukhara Jewish populations with relatively high prevalence of this disease. Since the oculo-pharyngeal muscular dystrophy prevalence was remarkably high in Southern Uruguay, a founder effect was hypothesized. To identify the ancestral haplotype we determined the (GCN) repeat number and the variants of four intragenic SNPs in Uruguayan OPMD families and a control sample. All families carrying the mutation (GCG)(11)(GCA)(3)(GCG) shared a common ancestral haplotype and the age of the mutation was estimated in 37-53 generations by a composite likelihood method. One family carrying the (GCG)(9)(GCA)(3)(GCG) allele had a different haplotype. The genealogical and molecular data suggested that the common ancestors were Canary Islands' settlers that arrived in Uruguay in the XIX century.
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PMID:(GCG)11 founder mutation in the PABPN1 gene of OPMD Uruguayan families. 1569 41

Trinucleotide repeat expansions have been associated with many neurodegenerative diseases, developmental disorders and muscular dystrophies. Among those triplet repeat expansions, polyalanine tract elongations are associated with early developmental abnormalities with the exception of OPMD, a late onset muscular dystrophy. This review presents an overview of recent advances on the molecular mechanisms underlying the group of polyalanine diseases and provides insights into the pathological impact of polyalanine tract expansion on protein dysfunction. While hydrophobic polyalanine tracts in the normal range are considered to be flexible spacers that confer stability and flexibility to the protein three-dimensional conformation, expanded polyalanine repeats are thought to destabilize the native conformation of the protein and alter protein levels and activity. Protein dysfunction following polyalanine expansion has been reported to cause transcriptional dysregulation which may delay early developmental processes or induce cytotoxicity in polyalanine disease models.
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PMID:Molecular mechanisms underlying polyalanine diseases. 1926 23