Details

Autor(en) / Beteiligte

• Pulkkinen, Leena
• Smith, Frances J. D.
• Shimizu, Hiroshi
• Murata, Satoru
• Yaoita, Hideo
• Hachisuka, Hiroshi
• Nishikawa, Takeji
• McLean, W. H. Irwin
• Uitto, Jouni

Titel

Homozygous Deletion Mutations in the Plectin Gene (PLEC1) in Patients with Epidermolysis Bullosa Simplex Associated with Late-Onset Muscular Dystrophy

Ist Teil von

• Human molecular genetics, 1996-10, Vol.5 (10), p.1539-1546

Ort / Verlag

Oxford: Oxford University Press

Erscheinungsjahr

1996

Quelle

Oxford Journals 2020 Medicine

Beschreibungen/Notizen

• In a distinct autosomal recessive variant of epidermolysis bullosa, EB-MD, life-long skin blistering is associated with late-onset muscular dystrophy of unknown etiology. Electron microscopy of these patients' skin suggests that tissue separation occurs intracellularly at the level of the hemidesmosomal inner plaque, which contains plectin, a high molecular weight cytoskeletal associated protein, also expressed in the sarcolemma of the muscle. In this study, we report two patients with EB-MD, each with a homozygous deletion mutation in the plectin gene, PLEC1. In the first case, the proband and her similarly affected sister had a homozygous 9 bp deletion mutation, designated as 2719del9, which resulted in elimination of three amino acids, QEA, in a sequence of 23 amino acids entirely conserved between the mouse and human sequences. The proband in the second family demonstrated a single nucleotide deletion at position 5866, designated as 5866delC, which resulted in frameshift and a premature termination codon for translation 16 bp downstream from the site of deletion. The absence of plectin in the hemidesmosomes, as reflected by negative immunofluorescence with an anti-plectin antibody (HD-1), associated with fragility of basal keratinocytes, implicates plectin as critical for binding of intermediate keratin filament network to hemidesmosomal complexes. The function of plectin as a putative attachment protein also in the muscle would explain the clinical phenotype consisting of cutaneous fragility and muscular dystrophy in EB-MD.