title: Novel compound heterozygous mutations in the plectin gene in epidermolysis bullosa with muscular dystrophy and the use of protein truncation test for detection of premature termination codon mutations.
abstract: Absence of plectin, a large cytoskeleton-associated protein expressed in the skin and muscle, has been shown to underlie epidermolysis bullosa with muscular dystrophy (EB-MD), an autosomal recessive disorder (OMIM No. 226670). In the present study, we report the case of a patient who presented with neonatal blistering and late-onset muscular dystrophy with nail and tooth abnormalities, as well as severe mucocutaneous involvement including laryngeal webs and urethral strictures, features not previously reported in this syndrome. Mutation detection, based on the use of heteroduplex analysis, revealed that the proband was a compound heterozygote for two plectin mutations, 4416delC/4359ins13, both resulting in premature termination codons in the plectin rod domain. Because these mutations, and the majority of those previously reported, reside within exon 32 of the plectin gene (PLEC1), we applied the protein truncation test (PTT) to screen for mutations in the two large 3' exons (nos. 32 and 33) of PLEC1, which together comprise approximately 75% of the coding region of the gene. PTT readily detected truncated polypeptides in the proband profiled in this study, as well as in a patient in whom we have previously identified premature termination codon mutations in exon 32. Thus, PTT provides a rapid and reliable strategy to identify premature termination codon mutations from genomic DNA within PLEC1.
authors.affiliation: Department of Dermatology, Jefferson Medical College and Jefferson Institute of Molecular Medicine, Thomas Jefferson University, Philadelphia, Pennsylvania 19107-5541, USA.
authors.forename: M
authors.initials: M
authors.lastname: Dang
authors.forename: L
authors.initials: L
authors.lastname: Pulkkinen
authors.forename: F J
authors.initials: FJ
authors.lastname: Smith
authors.forename: W H
authors.initials: WH
authors.lastname: McLean
authors.forename: J
authors.initials: J
authors.lastname: Uitto
mesh_terms: D000328:Adult; D001483:Base Sequence; D018388:Codon, Terminator / Q000235:genetics*; D004252:DNA Mutational Analysis / Q000379:methods; D004820:Epidermolysis Bullosa / Q000150:complications / Q000175:diagnosis / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D007381:Intermediate Filament Proteins / Q000235:genetics*; D008297:Male; D008969:Molecular Sequence Data; D009136:Muscular Dystrophies / Q000150:complications / Q000175:diagnosis / Q000235:genetics*; D009154:Mutation / Q000235:genetics*; D010375:Pedigree; D051190:Plectin; D011110:Polymorphism, Genetic / Q000235:genetics
chemical_list: D018388:Codon, Terminator; D007381:Intermediate Filament Proteins; C495332:PLEC protein, human; D051190:Plectin