Academic Journal
Loss of plectin causes epidermolysis bullosa with muscular dystrophy: cDNA cloning and genomic organization.
| العنوان: | Loss of plectin causes epidermolysis bullosa with muscular dystrophy: cDNA cloning and genomic organization. |
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| المؤلفون: | McLean, W H, Pulkkinen, L, Smith, F J, Rugg, E L, Lane, E B, Bullrich, F, Burgeson, R E, Amano, S, Hudson, D L, Owaribe, K, McGrath, J A, McMillan, J R, Eady, R A, Leigh, I M, Christiano, A M, Uitto, J |
| بيانات النشر: | Cold Spring Harbor Laboratory Press |
| سنة النشر: | 1996 |
| المجموعة: | HighWire Press (Stanford University) |
| مصطلحات موضوعية: | Research Papers |
| الوصف: | Plectin is a widely expressed high molecular weight protein that is involved in cytoskeleton-membrane attachment in epithelial cells, muscle, and other tissues. The human autosomal recessive disorder epidermolysis bullosa with muscular dystrophy (MD-EBS) shows epidermal blister formation at the level of the hemidesmosome and is associated with a myopathy of unknown etiology. Here, plectin was found to be absent in skin and cultured keratinocytes from an MD-EBS patient by immunofluorescence and immunoprecipitation, suggesting that plectin is a candidate gene/protein system for MD-EBS mutation. The 14800-bp human plectin cDNA was cloned and sequenced. The predicted 518-kD polypeptide has homology to the actin-binding domain of the dystrophin family at the amino terminus, a central rod domain, and homology to the intermediate filament-associated protein desmoplakin at the carboxyl terminus. The corresponding human gene (PLEC1), consisting of 33 exons spanning >26 kb of genomic DNA was cloned, sequenced, and mapped to chromosomal band 8q24. Homozygosity by descent was observed in the consanguineous MD-EBS family with intragenic plectin polymorphisms. Direct sequencing of PCR-amplified plectin cDNA from the patient's keratinocytes revealed a homozygous 8-bp deletion in exon 32 causing a frameshift and a premature termination codon 42 bp downstream. The clinically unaffected parents of the proband were found to be heterozygous carriers of the mutation. These results establish the molecular basis of MD-EBS in this family and clearly demonstrate the important structural role for plectin in cytoskeleton-membrane adherence in both skin and muscle. |
| نوع الوثيقة: | text |
| وصف الملف: | text/html |
| اللغة: | English |
| Relation: | http://genesdev.cshlp.org/cgi/content/short/10/14/1724; http://dx.doi.org/10.1101/gad.10.14.1724 |
| DOI: | 10.1101/gad.10.14.1724 |
| الاتاحة: | http://genesdev.cshlp.org/cgi/content/short/10/14/1724 https://doi.org/10.1101/gad.10.14.1724 |
| Rights: | Copyright (C) 1996, Cold Spring Harbor Laboratory Press |
| رقم الانضمام: | edsbas.A577CF29 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1101/gad.10.14.1724 |
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