Objective: Epidermolysis bullosa associated with muscular dystrophy (EB-MD) is a rare, autosomal recessive form of epidermolysis bullosa simplex caused by mutations in PLEC1. We describe a mild case due to compound heterozygous mutations in PLEC1, (2677del9 and the novel mutation Q1644X).
Methods: Clinical, pathological and mutation analysis findings are described.
Results: The patient is a 40 year old male who presented with slowly progressive weakness from age 28. Clinical features include mild skin blistering since birth, late-onset upper limb predominant weakness, facial weakness, partial ptosis, incomplete ophthalmoplegia and paroxysmal atrial fibrillation. Skin immunofluorescence mapping showed significantly reduced and fragmented staining of plectin at the dermal-epidermal basement membrane. Plectin staining in muscle showed increased staining of the cytoplasm and sarcolemma of type 1 fibres, and decreased staining of type 2 fibres. Desmin staining was significantly reduced in the sarcolemma with abnormal inclusion bodies in the cytoplasm. Mutation analysis revealed compound heterozygosity for a novel spontaneous paternal nonsense mutation 4930C>T/Q1644X in exon 31, and a previously reported maternal deletion (2677del9/893del3) in exon 21. This in-frame deletion may convey a milder clinical phenotype due the presence of partially functional protein. Most previous cases of EB-MD have been due to nonsense or frame-shift mutations with downstream premature termination codons on both alleles.
Conclusions: This is the first Australian case of EB-MD with a novel mutation in one allele. This case demonstrates a mild clinical phenotype and highlights the unusual clinical phenotype of EB-MD.