Homozygous deletion mutations in the plectin gene (PLEC1) in patients with epidermolysis bullosa simplex associated with late-onset muscular dystrophy

被引:130
作者
Pulkkinen, L
Smith, FJD
Shimizu, H
Murata, S
Yaoita, H
Hachisuka, H
Nishikawa, T
McLean, WHI
Uitto, J
机构
[1] JEFFERSON MED COLL,DEPT DERMATOL & CUTANEOUS BIOL,PHILADELPHIA,PA 19107
[2] JEFFERSON MED COLL,DEPT BIOCHEM & MOL PHARMACOL,PHILADELPHIA,PA 19107
[3] UNIV DUNDEE,CRC,CELL STRUCT RES GRP,DUNDEE,SCOTLAND
[4] KEIO UNIV,SCH MED,DEPT DERMATOL,TOKYO,JAPAN
[5] JICHI MED SCH,DEPT DERMATOL,MINAMI KAWACHI,TOCHIGI 32904,JAPAN
[6] KURUME UNIV,SCH MED,DEPT DERMATOL,KURUME,FUKUOKA 830,JAPAN
基金
英国惠康基金;
关键词
D O I
10.1093/hmg/5.10.1539
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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 2719de19, 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.
引用
收藏
页码:1539 / 1546
页数:8
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