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Case Reports
. 2006 May;43(5):e23.
doi: 10.1136/jmg.2005.037598.

Oculopharyngeal muscular dystrophy: a point mutation which mimics the effect of the PABPN1 gene triplet repeat expansion mutation

D O Robinson  1 , A J Wills, S R Hammans, S P Read, J Sillibourne
Affiliations
Case Reports

Oculopharyngeal muscular dystrophy: a point mutation which mimics the effect of the PABPN1 gene triplet repeat expansion mutation

D O Robinson et al. J Med Genet. 2006 May.

Abstract

Background: Oculopharyngeal muscular dystrophy (OPMD) is an autosomal dominant late onset neuromuscular disease characterised by proximal muscle weakness, ptosis, and swallowing difficulty. The only causative mutation described to date is a triplet repeat expansion consisting of two to seven additional base triplets in a repeat sequence in exon 1 of the polyadenine binding protein nuclear 1 (PABPN1) gene. This results in an increase in length of a polyalanine tract in the PABPN1 protein from 10 to 12-17 residues.

Objective: Description of another mutation in a case of OPMD.

Methods: Sequence analysis of exon 1 of the PABPN1 gene was undertaken on 202 patients referred for a possible diagnosis of OPMD but negative for the triplet repeat expansion mutation.

Results: A case was identified with typical symptoms of OPMD, negative for the repeat expansion mutation but with a missense mutation in PABPN1 close to the 3' end of the normal polyalanine codon repeat sequence.

Conclusions: The single base mutation changes a glycine codon to an alanine codon and results in an increase in the number of contiguous polyalanine codons. This mimics the effect of the common triplet repeat expansion mutation and represents a previously undescribed mechanism of mutation.

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Conflict of interest statement

Conflicts of interest: none declared

References

    1. Brais B, Bouchard J P, Xie Y G, Rochefort D L, Chretien N, Tome F M, Lafreniere R G, Rommens J M, Uyama E, Nohira O, Blumen S, Korczyn A D, Heutink P, Mathieu J, Duranceau A, Codere F, Fardeau M, Rouleau G A. Short GCG expansions in the PABP2 gene cause oculopharyngeal muscular dystrophy. Nat Genet 199818164–167. - PubMed
    1. Robinson D O, Hammans S R, Read S P, Sillibourne J. Oculopharyngeal muscular dystrophy (OPMD): Analysis of the PABPN1 gene expansion sequence in 86 patients reveals 13 different expansion types and further evidence for unequal recombination as the mutational mechanism. Hum Genet 2005116267–271. - PubMed
    1. Scacheri P C, Garcia C, Herbert R, Hofman E P. Unique PABP2 mutations in “Cajuns” suggest multiple founders of oculopharyngeal muscular dystrophy in populations with French ancestry. Am J Med Genet 199986477–481. - PubMed
    1. Van der Sluijs B M, van Engelen B G, Hoefsloot L H. Ooculopharyngeal muscular dystrophy due to a small duplication in the PABPN1 gene. Hum Mutat 200321553 - PubMed
    1. Miller S A, Dykes D D, Polesky H F. A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res 1988161215 - PMC - PubMed

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