RECESSIVE EPIDERMOLYSIS-BULLOSA SIMPLEX ASSOCIATED WITH PLECTIN MUTATIONS - INFANTILE RESPIRATORY COMPLICATIONS IN 2 UNRELATED CASES

Plectin is a 500 kDa protein involved in cytoskeleton-plasma membrane attachment with a wide tissue distribution including cutaneous and air way epithelia, muscle and neuronal tissue, Recently, mutations in the gene encoding plectin (PLEC1) have been implicated in the pathogenesis of an autosomal recessive variant of epidermolysis bullosa simplex in which cutaneous blistering starting in the neonatal period is associa ted with muscular dystrophy in later life, In this study, we report tw o unrelated patients, both of consanguineous parentage. who presented with cutaneous blistering and a hoarse cry fi ow. birth, Both experien ced inspiratory strider and respiratory distress, necessitating emerge ncy tracheostomy in one case, Immunoreactivity to monoclonal antibodie s against plectin was absent or markedly reduced in skin biopsies from both patients, Electron microscopy revealed a low intraepidermal plan e of cleavage and hypoplastic hemidesmosomes with a reduced associatio n with keratin intermediate filaments. Direct sequencing of PLEC1 in e ach case demonstrated two novel homozygous frameshift deletion mutatio ns, 5069del19 and 5905del2, which both create downstream premature ter mination codons, Although currently neither patient has symptoms of mu scle disease, the identification of mutations in PLEC1 may be predicti ve for the Future development of muscular dystrophy. Recessive epiderm olysis bullosa simplex resulting from abnormalities in plectin should be considered in the differential diagnosis of cutaneous blistering, h oarseness and strider in infancy.