+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

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



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



Laboratory Investigation; a Journal of Technical Methods and Pathology 78(2): 195-204



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.

Please choose payment method:






(PDF emailed within 1 workday: $29.90)

Accession: 009109940

Download citation: RISBibTeXText

PMID: 9484717


Related references

Novel compound heterozygous mutations in the plectin gene in epidermolysis bullosa with muscular dystrophy , and development of protein truncation test for detection of premature termination codon mutations. Journal of Investigative Dermatology 108(4): 562, 1997

Epidermolysis bullosa with muscular dystrophy A novel premature termination codon and de novo deletion mutations in the plectin gene. Journal of Investigative Dermatology 112(4): 615, 1999

Epidermolysis bullosa: novel and de novo premature termination codon and deletion mutations in the plectin gene predict late-onset muscular dystrophy. Journal of Investigative Dermatology 114(2): 381-387, 2000

Four novel plectin gene mutations in Japanese patients with epidermolysis bullosa with muscular dystrophy disclosed by heteroduplex scanning and protein truncation tests. Journal of Investigative Dermatology 112(1): 109-112, 1999

Novel compound heterozygous mutations in PLEC gene causing epidermolysis bullosa simplex with muscular dystrophy, case series of two affected sisters. Neuromuscular Disorders 27: S112-S113, 2017

Recurrent COL7A1 mutations in Japanese patients with dystrophic epidermolysis bullosa: positional effects of premature termination codon mutations on clinical severity. Japanese Collaborative Study Group on Epidermolysis Bullosa. Journal of Investigative Dermatology 112(6): 991-993, 1999

Compound heterozygosity for premature termination codon and glycine substitution mutations in the COL7A1 gene in Korean siblings with a moderately severe phenotype of recessive dystrophic epidermolysis bullosa. Journal of Dermatological Science 33(3): 180-183, 2003

Epidermolysis bullosa simplex with muscular dystrophy Cloning of the human plectin gene and pathogenic mutations in four families. American Journal of Human Genetics 59(4 SUPPL ): A38, 1996

Congenital muscular dystrophy, myasthenic symptoms and epidermolysis bullosa simplex (EBS) associated with mutations in the PLEC1 gene encoding plectin. Neuromuscular Disorders 20(11): 709-711, 2011

Homozygous deletion mutations in the plectin gene (PLEC1) in patients with epidermolysis bullosa simplex associated with late-onset muscular dystrophy. Human Molecular Genetics 5(10): 1539-1546, 1996

Compound heterozygous PLEC mutations in a patient of consanguineous parentage with epidermolysis bullosa simplex with muscular dystrophy and diffuse alopecia. International Journal of Dermatology 54(2): 185-187, 2015

Premature termination codon mutations in the type VII collagen gene in recessive dystrophic epidermolysis bullosa result in nonsense-mediated mRNA decay and absence of functional protein. Journal of Investigative Dermatology 109(3): 390-394, 1997

Downstream effects of plectin mutations in epidermolysis bullosa simplex with muscular dystrophy. Acta Neuropathologica Communications 4(1): 44, 2017

Novel premature termination codon mutations in the laminin gamma2-chain gene (LAMC2) in Herlitz junctional epidermolysis bullosa. Journal of Investigative Dermatology 111(6): 1233-1234, 1998

Premature termination codon mutations in the type VII collagen gene (COL7A1) underlie severe recessive dystrophic epidermolysis bullosa. Proceedings of the Association of American Physicians 107(2): 245-252, 1995