engleski

Oculopharyngeal muscular dystrophy - genotype studies in Croatian population

Oculopharyngeal muscular dystrophy (OPMD ; OMIM 164300) is a late-onset disorder characterised by progressive ptosis, dysphagia and proximal limb weakness. Dominant and recessive OPMD are caused by stable short (GCG)7-13 triplet repeat expansions in exon 1 of the poly(A)binding protein 2 gene (PABP2) ; normal repeat length beeng (GCG)6. The (GCG)7 allele is a polymorphism that acts as a modifier of severity of dominant OPMD, or as a recessive mutation. According to Brais (2001) this mutation has 1-2% prevalence in North America, France and Japan. In recent study performed on 201 normal individuals from United Kingdom (Hill et al. 2001) no (GCG)7 allele was detected. Our preliminary study of first six OPMD patients from Croatia enabled us to identify four different allelles with 7, 8, 9 and 11 (GCG) repeats. Based on these findings, we hypothesised that allele (GCG)7 might be frequent in Croatia. To validate our hypothesis, we have screened a control population of 500 samples from individuals with no known family history of OPMD for an expansion of (GCG) repeat using allele- specific PCR. One healthy heterozygote not related to previously detected patient with alleles (GCG)7, 8 was found suggesting the high frequency of 4% (2 /506 patients) of (GCG) 7 mutation in Croatia. In view of this, we may expect autosomal recessive homozygotes in our population. Patients with this form may be underdiagnosed because of a milder phenotype and the absence of clear family history. More extensive study should confirm these data.

oculopharyngeal muscular dystrophy; triplet repeat expansions; autosomal recessive homozygotes

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