Avtor/Urednik		Liović, Mirjana
Naslov		Mutacije v genih za keratine 5 in 14 pri bolnikih z epidermolysis bullosa simplex: povezava med strukturo in funkcijo
Prevedeni naslov		Keratin 5 and 14 gene mutations in epidermolysis bullosa simplex patients: genotype to phenotype correlations
Tip		monografija
Kraj izdaje		Ljubljana
Založnik		Medicinska fakulteta
Leto izdaje		1999
Obseg		str. 109
Jezik		slo
Abstrakt		Epidermolysis bullosa simplex (EBS) is one of the most studied and documented hereditary skin disorders. It is based upon skin fragility due to mutations affecting the genes encoding of human K5 and K14. The identification of more than 50 different mutations related to EBS, has given much information about the role that different regions of keratins have in intermediate filament assembly and function. It has been proposed that the three most frequent types of EBS, WC (Weber-Cockayne), K (Kobner) and DM (Dowling-Meara), are caused by mutations within specific regions of K5 and K14. Thus, EBS-DM (severe phenotype) is caused by mutations in the 1A and 2B helix of the protein, while the mild EBS-WC phenotype is caused by mutations in other sites, such as the L12 linker region. The results of our own findings on EBS patients in part support this theory. Fifteen families with a history of EBS have been included in our study. Genomic DNA of patients and their healthy relatives was analysed for k% and K14 gene mutations. Initially, we sequenced the 1A, L12, 2B hot-spot encoding regions but subsequently extended it to the entire coding portion of the two genes. Six novel mutations were identified, four in K5 and two in K14. In K5, three are located in 1A region: N177S, V186L and T 198S, and one, D328E, is in the L12 linker. In K14, V133L lies in 1A helix, while the three-nucleotide deletion, deltaE411, is at the end of 2B helix. Molecular modelling of K5/K14 1A helix, protein seconadry structure predictions and evaluation of published data helped us predict the possible effect of each of these mutations on keratin protein structure and function. In addition, we also monitored assembly of mutant keratins into the intermediate filament network and subjevted them to thermal stress to establish the effect of the mutations on filament stability. (Abstract truncated at 2000 characters).
Deskriptorji		EPIDERMOLYSIS BULLOSA KERATIN POLYMERASE CHAIN REACTION PHENOTYPE PEDIGREE DNA PRIMERS MODELS, MOLECULAR