Universität zu Köln

Blaydon, Diana C., Nitoiu, Daniela, Eckl, Katja-Martina, Cabral, Rita M., Bland, Philip, Hausser, Ingrid, van Heel, David A., Rajpopat, Shefali, Fischer, Judith ORCID: 0000-0002-8580-8118, Oji, Vinzenz ORCID: 0000-0003-1380-4828, Zvulunov, Alex, Traupe, Heiko, Hennies, Hans Christian and Kelsell, David P. (2011). Mutations in CSTA, Encoding Cystatin A, Underlie Exfoliative Ichthyosis and Reveal a Role for This Protease Inhibitor in Cell-Cell Adhesion. Am. J. Hum. Genet., 89 (4). S. 564 - 572. CAMBRIDGE: CELL PRESS. ISSN 0002-9297

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Abstract

Autosomal-recessive exfoliative ichthyosis presents shortly after birth as dry, scaly skin over most of the body with coarse peeling of non-erythematous skin on the palms and soles, which is exacerbated by excessive moisture and minor trauma. Using whole-genome homozygosity mapping, candidate-gene analysis and deep sequencing, we have identified loss-of-function mutations in the gene for protease inhibitor cystatin A (CSTA) as the underlying genetic cause of exfoliative ichthyosis. We found two homozygous mutations, a splice-site and a nonsense mutation, in two consanguineous families of Bedouin and Turkish origin. Electron microscopy of skin biopsies from affected individuals revealed that the level of detachment occurs in the basal and lower suprabasal layers. In addition, in vitro modeling suggests that in the absence of cystatin A protein, there is a cell-cell adhesion defect in human keratinocytes that is particularly prominent when cells are subject to mechanical stress. We show here evidence of a key role for a protease inhibitor in epidermal adhesion within the lower layers of the human epidermis.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Blaydon, Diana C. UNSPECIFIED UNSPECIFIED UNSPECIFIED Nitoiu, Daniela UNSPECIFIED UNSPECIFIED UNSPECIFIED Eckl, Katja-Martina UNSPECIFIED UNSPECIFIED UNSPECIFIED Cabral, Rita M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Bland, Philip UNSPECIFIED UNSPECIFIED UNSPECIFIED Hausser, Ingrid UNSPECIFIED UNSPECIFIED UNSPECIFIED van Heel, David A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Rajpopat, Shefali UNSPECIFIED UNSPECIFIED UNSPECIFIED Fischer, Judith UNSPECIFIED orcid.org/0000-0002-8580-8118 UNSPECIFIED Oji, Vinzenz UNSPECIFIED orcid.org/0000-0003-1380-4828 UNSPECIFIED Zvulunov, Alex UNSPECIFIED UNSPECIFIED UNSPECIFIED Traupe, Heiko UNSPECIFIED UNSPECIFIED UNSPECIFIED Hennies, Hans Christian UNSPECIFIED UNSPECIFIED UNSPECIFIED Kelsell, David P. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-487420
DOI:	10.1016/j.ajhg.2011.09.001
Journal or Publication Title:	Am. J. Hum. Genet.
Volume:	89
Number:	4
Page Range:	S. 564 - 572
Date:	2011
Publisher:	CELL PRESS
Place of Publication:	CAMBRIDGE
ISSN:	0002-9297
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language NETHERTON-SYNDROME; ATOPIC-DERMATITIS; SKIN BARRIER; STEFIN-A; ASSOCIATION; DISEASE; LEADS; KERATINOCYTES; ENVIRONMENT; MATRIPTASE Multiple languages Genetics & Heredity Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/48742