Netherton Syndrome: A Genotype-Phenotype Review

Netherton syndrome (OMIM #256500) is a rare but severe autosomal recessive form of ichthyosis that affects the skin, hair, and immune system. The identification of SPINK5 , which encodes for the serine protease inhibitor LEKTI, as the gene responsible for Netherton syndrome, enabled the search for c...

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Bibliographic Details
Published in:Molecular diagnosis & therapy 2017-04, Vol.21 (2), p.137-152
Main Authors: Sarri, Constantina A., Roussaki-Schulze, Angeliki, Vasilopoulos, Yiannis, Zafiriou, Efterpi, Patsatsi, Aikaterini, Stamatis, Costas, Gidarokosta, Polyxeni, Sotiriadis, Dimitrios, Sarafidou, Theologia, Mamuris, Zissis
Format: Article
Language:English
Subjects:
Biomedical and Life Sciences
Biomedicine
Cancer Research
Congenital diseases
Consanguinity
Gene expression
Genotype & phenotype
Genotypes
Hair
Human Genetics
Ichthyosis
Immune system
Laboratory Medicine
Molecular Medicine
mRNA turnover
Mutation
Netherton syndrome
Neutrophils
Nonsense-mediated mRNA decay
Patients
Pharmacotherapy
Post-transcription
Prenatal diagnosis
Proteases
Review Article
Serine
Serine proteinase
Skin
Splicing
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Summary:Netherton syndrome (OMIM #256500) is a rare but severe autosomal recessive form of ichthyosis that affects the skin, hair, and immune system. The identification of SPINK5 , which encodes for the serine protease inhibitor LEKTI, as the gene responsible for Netherton syndrome, enabled the search for causative mutations in Netherton syndrome patients and families. However, information regarding these mutations and their association with the pathological Netherton syndrome phenotype is scarce. Herein, we provide an up-to-date overview of 80 different mutations in exonic as well as intronic regions that have been currently identified in 172 homozygous or compound heterozygous patients from 144 families. Genotypes with mutations located more upstream in LEKTI correlate with more severe phenotypes compared with similar mutations located towards the 3′ region. Furthermore, splicing mutations and post-transcriptional mechanism of nonsense-mediated mRNA decay affect LEKTI expression in variable ways. Genotype–phenotype correlations form the basis of prenatal diagnosis in families with a history of Netherton syndrome and when consanguinity is implied.
ISSN:1177-1062
1179-2000
DOI:10.1007/s40291-016-0243-y