Novel and recurrent mutations in keratin 10 causing bullous congenital ichthyosiform erythroderma

AA, causing two amino acid substitutions, D155E and R156S, also in the 1A domain of the K10 polypeptide. In 2 further kindreds, the previously reported "hotspot" mutations 2139C-->T and 2140G-->A were found. These mutations predict amino acid substitutions in the helix 1A domain of K10, designated R156C and R156H respectively. The proband in the fourth family was found to carry a novel mutation 4724T-->C, predicting the amino acid change L452P in the helix 2B domain of K10. All mutations were confirmed in the affected persons and were excluded from a population of 50 normal, unrelated individuals by restriction enzyme analysis. The location of these mutations in the highly conserved helix boundary motif sequences of K10 are consistent with previously reported dominant negative mutations in K10 and other keratins. Despite the unusual nature of two of these mutations, in particular the double missense mutation, the phenotypes of the affected individuals in these 4 families were entirely typical of BCIE. -->

ISSN:	1600-0625 0906-6705
DOI:	10.1111/j.1600-0625.1999.tb00358.x
Přístupová URL adresa:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::2cef0ad967e5ad6b60f445d78ea6271e https://doi.org/10.1111/j.1600-0625.1999.tb00358.x
Rights:	CLOSED
Přírůstkové číslo:	edsair.doi.dedup.....2cef0ad967e5ad6b60f445d78ea6271e
Autor:	E. B. Lane, M. White, Paul E. Bowden, Caroline Higgins, Whi McLean, Irene M. Leigh, S.M. Morley
Rok vydání:	1999
Předmět:	Male Proband Congenital ichthyosiform erythroderma Population Hyperkeratosis Mutation Missense Erythroderma Dermatology Biology Biochemistry Epidermolytic hyperkeratosis Automation medicine Humans Missense mutation education Transversion Molecular Biology Genetics education.field_of_study Base Sequence integumentary system Genetic Carrier Screening Exons Ichthyosiform Erythroderma Congenital medicine.disease Pedigree Amino Acid Substitution Keratins Female
Zdroj:	Experimental Dermatology. 8:120-123
ISSN:	1600-0625 0906-6705
DOI:	10.1111/j.1600-0625.1999.tb00358.x
Popis:	Bullous congenital ichthyosiform erythroderma (BCIE) is a dominantly inherited keratinizing disorder characterized by erythroderma and blistering in neonates and generalized epidermolytic hyperkeratosis (EH) in adulthood. Previously, it has been shown that BCIE can be caused by mutations in either of the genes encoding K1 or K10, the keratins predominantly expressed in suprabasal layers of the epidermis. Using direct sequencing of genomic PCR fragments, we have analyzed 4 British families with BCIE, all of whom were found to carry mutations in K10. In 1 family, the affected person was found to have an unusual dinucleotide transversion mutation, 2138CC-->AA, causing two amino acid substitutions, D155E and R156S, also in the 1A domain of the K10 polypeptide. In 2 further kindreds, the previously reported "hotspot" mutations 2139C-->T and 2140G-->A were found. These mutations predict amino acid substitutions in the helix 1A domain of K10, designated R156C and R156H respectively. The proband in the fourth family was found to carry a novel mutation 4724T-->C, predicting the amino acid change L452P in the helix 2B domain of K10. All mutations were confirmed in the affected persons and were excluded from a population of 50 normal, unrelated individuals by restriction enzyme analysis. The location of these mutations in the highly conserved helix boundary motif sequences of K10 are consistent with previously reported dominant negative mutations in K10 and other keratins. Despite the unusual nature of two of these mutations, in particular the double missense mutation, the phenotypes of the affected individuals in these 4 families were entirely typical of BCIE.
Databáze:	OpenAIRE
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