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Netherton Syndrome: A Genotype-Phenotype Review

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Abstract

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.

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Authors and Affiliations

  1. Laboratory of Genetics, Comparative and Evolutionary Biology, Department of Biochemistry and Biotechnology, University of Thessaly, Ploutonos 26 and Aiolou, 41221, Larissa, Greece

    Constantina A. Sarri, Yiannis Vasilopoulos, Costas Stamatis, Theologia Sarafidou & Zissis Mamuris

  2. Department of Dermatology, University General Hospital Larissa, University of Thessaly, Larissa, Greece

    Angeliki Roussaki-Schulze, Efterpi Zafiriou & Polyxeni Gidarokosta

  3. Second Department of Dermatology, School of Medicine, Aristotle University, Papageorgiou Hospital, Thessaloniki, Greece

    Aikaterini Patsatsi & Dimitrios Sotiriadis

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  1. Constantina A. Sarri
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Authors C. A. Sarri, A. Roussaki-Schulze, Y. Vasilopoulos, E. Zafiriou, A. Patsatsi, C. Stamatis, P. Gidarokosta, D. Sotiriadis, T. Sarafidou, and Z. Mamuris declare that they have no conflicts of interest.

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Funding was received from Postgraduate Courses “Biotechnology—Quality Assessment in Nutrition and the Environment” and “Applications of Molecular Biology—Genetics—Diagnostic Biomarkers” of the Department of Biochemistry and Biotechnology, University of Thessaly, Larissa, Greece.

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Sarri, C.A., Roussaki-Schulze, A., Vasilopoulos, Y. et al. Netherton Syndrome: A Genotype-Phenotype Review. Mol Diagn Ther 21, 137–152 (2017). https://doi.org/10.1007/s40291-016-0243-y

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