Abstract
Purpose::
Oculopharingeal muscular dystrophy (OPMD) is an autosomal dominant disease mainly characterized by a late-onset triad of progressive ptosis, dysphagia and distal limb weakness. The disease is caused by expansions of a (GCG)6 triplet repeat in exon 1 of the PABPN1 gene, located at 14q11. Abnormal GCG expansions vary between 8 to 13 (GCG) triplets but there is no genotype-phenotype correlation in populations studied to date. The (GCG)9 allele has been the most prevalently found in individuals from several ethnic groups. In this work we describe the molecular analysis of PABPN1 gene in 16 unrelated mexican propositus with a clinical diagnosis of OPMD.
Methods::
Sixteen patients from different Mexican unrelated families with diagnosis of OPMD, were included. Evaluation included complete ophthalmological examination. After informed consent, DNA was obtained from peripheral blood leukocytes and a fragment of the PABPN1 gene exon 1 containing the GCG tract, was amplified by PCR . The products of amplification were cloned into plasmid vectors using a TA cloning strategy. We also characterize two intragenic SNPs by direct sequencing.
Results::
Of 16 OPMD patients, 10 (62.5%) presented a PABPN1 (GCG)11 allele, while the remaining 6 exhibited a (GCG)9 allele. All patients harbouring the (GCG)11 allele shared a same haplotype for PABPN1, indicating a founder effect. There were no evident clinical differences between patients with (GCG)11 and (GCG)9 .
Conclusions::
In OPMD the heterozygote mutation more frequently found in several studies has been (GCG)9 (Brais B. 2003), in our Mexican population the most frequent mutation is (GCG)11. Our results indicate that PABPN1 (GCG)11 is the most common OPMD causing allele in Mexican population. This results contrast with reports in other populations in wich (GCG)9 is the most prevalent.SNP analysis indicate that the (GCG)11 allele is a founder mutation, as all affected individuals with this allele share a common PABPN1 haplotype. No apparent genotype-phenotype correlation was observed in our study
Keywords: mutations • degenerations/dystrophies • eyelid