Medizinische Universität Graz - Research portal
Selected Publication:
SHR Neuro Cancer Cardio Lipid Metab Microb
Raghunath, M; Tontsidou, L; Oji, V; Aufenvenne, K; Schürmeyer-Horst, F; Jayakumar, A; Ständer, H; Smolle, J; Clayman, GL; Traupe, H.
SPINK5 and Netherton syndrome: novel mutations, demonstration of missing LEKTI, and differential expression of transglutaminases.
J Invest Dermatol. 2004; 123(3):474-483
Doi: 10.1111/j.0022-202X.2004.23220.x
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- Co-authors Med Uni Graz
- Smolle Josef
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- Abstract:
- Netherton syndrome (NTS) is an autosomal recessive congenital ichthyosis featuring chronic inflammation of the skin, hair anomalies, epidermal hyperplasia with an impaired epidermal barrier function, failure to thrive and atopic manifestations. The disease is caused by mutations in the SPINK5 gene encoding the serine proteinase inhibitor lympho-epithelial Kazal-type inhibitor (LEKTI). Sequence analyses of SPINK5 in seven NTS patients from five different families allowed us to identify two known and three novel mutations all creating premature termination codons. We developed a monoclonal antibody giving a strong signal for LEKTI in the stratum granulosum of normal skin and demonstrated absence of the protein in NTS epidermis. Immunoblot analysis revealed presence of full length LEKTI and of LEKTI cleavage fragments in normal hair roots, whereas in NTS hair roots LEKTI and its cleavage products were completely missing. Transglutaminase1 activity was present throughout almost the entire suprabasal epidermis in NTS, whereas in normal skin it is restricted to the stratum granulosum. In contrast, immunostaining for transglutaminase3 was absent or faint. Moreover, comparable with the altered pattern in psoriatic skin the epidermis in NTS strongly expressed the serine proteinase inhibitor SKALP/elafin and the anti-microbial protein human beta-defensin 2. These studies demonstrate LEKTI deficiency in the epidermis and in hair roots at the protein level and an aberrant expression of other proteins, especially transglutaminase1 and 3, which may account for the impaired epidermal barrier in NTS.
- Find related publications in this database (using NLM MeSH Indexing)
- Adult -
- Amino Acid Sequence -
- Antibodies, Monoclonal -
- Base Sequence -
- Biological Markers -
- Calcium-Binding Proteins - genetics
- Carrier Proteins - genetics
- Cell Differentiation - genetics
- Codon, Nonsense - genetics
- Epidermis - enzymology
- Female - enzymology
- Gene Expression Regulation, Enzymologic - enzymology
- Humans - enzymology
- Ichthyosiform Erythroderma, Congenital - genetics
- Infant, Newborn - genetics
- Male - genetics
- Molecular Sequence Data - genetics
- Mutation - genetics
- Pedigree - genetics
- Syndrome - genetics
- Transglutaminases - genetics
- Find related publications in this database (Keywords)
- elafin
- epidermal barrier
- genetics
- human beta-defensin 2
- mutation
- Netherton syndrome
- serine proteinases
- skin
- transglutaminase