A South African family with oculopharyngeal muscular dystrophy: Clinical and molecular genetic characteristics

Abstract

Autosomal dominantly inherited oculopharyngeal muscular dystrophy (OPMD) is caused by a trinucleotide repeat expansion in exon 1 of the polyadenylate binding protein nuclear 1 (PABPN1) gene on chromosome 14q. A large family with OPMD was recently identified in Pretoria, South Africa (SA). Molecular studies revealed a (GCG)11(GCA)3GCG or (GCN)15 mutant allele. The (GCN)15 mutation detected in this family has been described previously in families from Uruguay and Mexico as a founder effect. To our knowledge, this is the first report of an SA Afrikaner family with molecularly confirmed OPMD. The proband, a 64-year-old woman, presented to the neurology outpatient department at Steve Biko Academic Hospital, Pretoria. A sibship of 18 individuals was identified, of whom eight had OPMD. Four patients were interviewed and examined clinically, and electromyographic studies were performed. Molecular analysis of the PABPN1 gene was performed by polymerase chain reaction amplification and direct sequencing of exon 1 in three of the patients. Patients presented with ptosis, external ophthalmoplegia, dysphagia, dysarthria and mild proximal weakness. High foot arches and absent ankle reflexes raised the possibility of peripheral neuropathy, but electromyography showed only mildly low sensory amplitudes, and myopathic units in two patients.

Understanding the genetic diversity of South Africa’s peoples

“…This is well demonstrated by two articles in this issue of the SAMJ. [1,2] Apart from research opportunities, this diversity of genetic disease has major relevance when offering diagnostic testing. Frequencies of disease may differ between groups, and the mutational basis may be different.…”

“…There are many diseases for which such founder mutations have been described in the Afrikaner population, including porphyria variegata, familial hypercholesterolaemia, Fanconi's anaemia, Gaucher disease and autosomal recessive polycystic kidney disease. [7][8][9][10][11] In this issue, Schutte et al [1] report a rare dynamic repeat disorder, oculopharyngeal muscular dystrophy (OPMD), for the first time in a family with Afrikaner ancestry. Preliminary evidence, not surprisingly, suggests a founder effect.…”