RESUMO
Oculopharyngeal muscular dystrophy is a neuromuscular disease usually presenting in the 5th or 6th decades of life with a dominant inheritance pattern. In almost all cases the cause of the disease is the expansion of a DNA repeat sequence containing GCG and GCA codons in exon 1 of the PABPN1 gene from 10 to between 12 and 17 repeats. However one case has been previously reported without the gene expansion but instead with a c.35G>C missense mutation converting a glycine codon to an alanine and resulting in a sequence of 13 contiguous alanine codons, thus mimicking the effect of the common expansion mutation. Here we report two further cases of OPMD caused by the c.35G>C point mutation. Clinical and pedigree data indicate the usual OPMD dominant inheritance pattern.
Assuntos
Alanina/genética , Glicina/genética , Distrofia Muscular Oculofaríngea/genética , Mutação Puntual/genética , Proteína II de Ligação a Poli(A)/genética , Idoso , Análise Mutacional de DNA , Feminino , Humanos , Masculino , Músculo Esquelético/patologia , Distrofia Muscular Oculofaríngea/patologiaRESUMO
We have previously described individuals presenting with transient neonatal diabetes and showing a variable pattern of DNA hypomethylation at imprinted loci throughout the genome. We now report mutations in ZFP57, which encodes a zinc-finger transcription factor expressed in early development, in seven pedigrees with a shared pattern of mosaic hypomethylation and a conserved range of clinical features. This is the first description of a heritable global imprinting disorder that is compatible with life.