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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 [approximate]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. |
