caa a22 4500 397574258 CHVBK 20180308164850.0 cr unu---uuuuu 161202e199610 xx s 000 0 eng 10.1093/hmg/5.10.1539 doi (NATIONALLICENCE)oxford-10.1093/hmg/5.10.1539 Homozygous Deletion Mutations in the Plectin Gene (PLEC1) in Patients with Epidermolysis Bullosa Simplex Associated with Late-Onset Muscular Dystrophy [Elektronische Daten] [Leena Pulkkinen, Frances J. D. Smith, Hiroshi Shimizu, Satoru Murata, Hideo Yaoita, Hiroshi Hachisuka, Takeji Nishikawa, W. H. Irwin McLean, Jouni Uitto] 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. © 1996 Oxford University Press Pulkkinen Leena Departments of Dermatology and Cutaneous Biology, and Biochemistry and Molecular Pharmacology, Jefferson Medical College, 233 South 10th Street, Suite 450, Philadelphia, PA 19107-5541, USA aut Smith Frances J. D. CRC Cell Structure Research Group, University of Dundee, Dundee, UK aut Shimizu Hiroshi Department of Dermatology, Keio University School of Medicine, Tokyo, Japan aut Murata Satoru Department of Dermatology, Jichii Medical School, Minamikawach-Machi, Japan aut Yaoita Hideo Department of Dermatology, Jichii Medical School, Minamikawach-Machi, Japan aut Hachisuka Hiroshi Department of Dermatology, Kurume University School of Medicine, Kurume, Japan aut Nishikawa Takeji Department of Dermatology, Keio University School of Medicine, Tokyo, Japan aut McLean W. H. Irwin CRC Cell Structure Research Group, University of Dundee, Dundee, UK aut Uitto Jouni Departments of Dermatology and Cutaneous Biology, and Biochemistry and Molecular Pharmacology, Jefferson Medical College, 233 South 10th Street, Suite 450, Philadelphia, PA 19107-5541, USA aut Human Molecular Genetics Oxford University Press 5/10(1996-10), 1539-1546 0964-6906 5:10<1539 1996 5 hmg https://doi.org/10.1093/hmg/5.10.1539 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1093/hmg/5.10.1539 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Pulkkinen Leena Departments of Dermatology and Cutaneous Biology, and Biochemistry and Molecular Pharmacology, Jefferson Medical College, 233 South 10th Street, Suite 450, Philadelphia, PA 19107-5541, USA aut NATIONALLICENCE 700 1- Smith Frances J. D. CRC Cell Structure Research Group, University of Dundee, Dundee, UK aut NATIONALLICENCE 700 1- Shimizu Hiroshi Department of Dermatology, Keio University School of Medicine, Tokyo, Japan aut NATIONALLICENCE 700 1- Murata Satoru Department of Dermatology, Jichii Medical School, Minamikawach-Machi, Japan aut NATIONALLICENCE 700 1- Yaoita Hideo Department of Dermatology, Jichii Medical School, Minamikawach-Machi, Japan aut NATIONALLICENCE 700 1- Hachisuka Hiroshi Department of Dermatology, Kurume University School of Medicine, Kurume, Japan aut NATIONALLICENCE 700 1- Nishikawa Takeji Department of Dermatology, Keio University School of Medicine, Tokyo, Japan aut NATIONALLICENCE 700 1- McLean W. H. Irwin CRC Cell Structure Research Group, University of Dundee, Dundee, UK aut NATIONALLICENCE 700 1- Uitto Jouni Departments of Dermatology and Cutaneous Biology, and Biochemistry and Molecular Pharmacology, Jefferson Medical College, 233 South 10th Street, Suite 450, Philadelphia, PA 19107-5541, USA aut NATIONALLICENCE 773 0- Human Molecular Genetics Oxford University Press 5/10(1996-10), 1539-1546 0964-6906 5:10<1539 1996 5 hmg Metadata rights reserved CC BY-NC-4.0 http://creativecommons.org/licenses/by-nc/4.0 nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-oxford