| Co-Investigator(Kenkyū-buntansha) |
AKIYAMA Masashi Hokkaido Univ. Medical Hospital, Lec., 大学院・医学研究科, 講師 (60222551)
MATSUMURA Tetsuri Hokkaido Univ., Grad. School of Med., Inst., 大学院・医学研究科, 助手 (80301878)
AMAGAI Masayuki Keio Univ., School of Med., Assistant Prof., 医学部, 専任講師 (90212563)
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| Research Abstract |
Epidermolysis bullosa simplex associated with muscular dystrophy (EBS-MD ; OMIM# 226670) is an autosomal recessive disorder caused by genetic defects in the plectin gene. Because EBS-MD is rare, the precise phenotype-genotype correlation has not yet been fully elucidated. The purpose of this study was to define clinical features of EBS-MD and to further clarify its phenotype-genotype correlation. Clinical, ultrastructural, immunohistochemical and molecular features of 4 unrelated Japanese patients with EBS-MD were recorded. In addition, 6 cases with defined plectin gene mutations in the literature were reviewed. In the skin of EBS-MD, the blister formation always occurs just above the hemidesmosomes, and expression of plectin is absent or reduced in all cases examined. All 10 patients, including 6 cases in the literature, showed generalized blistering at birth or soon thereafter, and developed nail deformities. In addition, decayed teeth (5), urethral strictures (3), mild palmoplantar
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hyperkeratosis (2), infantile respiratory complications (2), alopecia (1) and laryngeal webs (1) were present. All 8 patients who were older than 9 years of age demonstrated considerable muscle weakness, and majority of them ended up being wheelchair bound. Among the 10 patients, 7 were products of consanguineous marriage, 9 have premature termination codon mutations in both alleles of plectin gene, and 7 cases were homozygous for the mutation. One patient who is homozygous for a 2719del9 inframe deletion mutation resulted in elimination of three amino acids, QEA, could still walk at the age of 46 and showed milder clinical severity. In conclusion, majority of patients were products of consanguineous marriage and have homozygous plectin gene mutations. Whereas patients with premature termination codon mutations in both alleles showed typically severe clinical features of EBS-MD and ended up to be wheelchair bound, a homozygote for an inframe deletion mutations showed positive, yet attenuated, plectin expression and milder clinical phenotype. Less
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