Clinical heterogeneity in recessive epidermolysis bullosa due to mutations in the keratin 14 gene, KRT14
| Autor: | Eleni Yiasemides, Ningning Dang, George Varigos, Dedee F. Murrell, Penelope Marr, Kim Tran, S. Klingberg, W. Melbourne, Niken Trisnowati, David Orchard, Chung Wo Chow, John C Su |
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| Rok vydání: | 2008 |
| Předmět: |
Proband
Pathology medicine.medical_specialty Keratin 14 Turkey Fluorescent Antibody Technique Genes Recessive Dermatology Biology Consanguinity Epidermolysis bullosa simplex Genotype-phenotype distinction Keratin medicine Humans Child Skin Genetics chemistry.chemical_classification integumentary system Keratin-16 Homozygote Australia Keratin-14 Keratin-6 Autosomal dominant trait medicine.disease Pedigree Keratin 5 Phenotype chemistry Mutation Female Epidermolysis bullosa Epidermolysis Bullosa Gene Deletion |
| Zdroj: | Clinical and Experimental Dermatology. 33:689-697 |
| ISSN: | 1365-2230 0307-6938 |
| DOI: | 10.1111/j.1365-2230.2008.02858.x |
| Popis: | Summary Background. Epidermolysis bullosa simplex (EBS), the most common subtype of EB, is usually inherited as an autosomal dominant trait caused by mutations in either the keratin 5 (KRT5) or keratin 14 (KRT14) genes. Recessive EBS (R-EBS) is extremely rare. Methods. We present the first Australian patient diagnosed with R-EBS, to our knowledge, and a comprehensive review of genotypes and phenotypes of R-EBS reported cases. Results. The female proband, of Turkish descent with consanguineous parentage, was referred to us at the age of 8 years. Clinically, she had a severe phenotype including generalized blisters, mucosal involvement and EB naevi. Immunofluorescence mapping and electron microscopy were consistent with a diagnosis of EBS. Staining for Keratin 14 (K14) was negative. The basal layer, however, reacted with monoclonal antibodies to keratins 6 (K6) and 16 (K16). Mutation screening from genomic DNA showed that the proband was homozygous for the truncation mutation Y204X in exon 3 of KRT14, and both unaffected parents were heterozygous for a single KRT14 Y204X mutation. The phenotype of our patient is reported in more detail and with longer follow-up than those of others published in the literature. Discussion. The proband’s phenotype was severe as an infant but improved with age, suggesting that an alternative keratin is pairing with K5 in her skin to compensate for the loss of K14 – a novel biological compensatory mechanism. It is interesting that K6 and K16 were expressed, as these are normally positive in hyperproliferative skin disorders. |
| Databáze: | OpenAIRE |
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