title: Netherton Syndrome: A Genotype-Phenotype Review.
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.
authors.affiliation: Laboratory of Genetics, Comparative and Evolutionary Biology, Department of Biochemistry and Biotechnology, University of Thessaly, Ploutonos 26 and Aiolou, 41221, Larissa, Greece.
authors.forename: Constantina A
authors.initials: CA
authors.lastname: Sarri
authors.affiliation: Department of Dermatology, University General Hospital Larissa, University of Thessaly, Larissa, Greece.
authors.forename: Angeliki
authors.initials: A
authors.lastname: Roussaki-Schulze
authors.affiliation: Laboratory of Genetics, Comparative and Evolutionary Biology, Department of Biochemistry and Biotechnology, University of Thessaly, Ploutonos 26 and Aiolou, 41221, Larissa, Greece.
authors.forename: Yiannis
authors.initials: Y
authors.lastname: Vasilopoulos
authors.affiliation: Department of Dermatology, University General Hospital Larissa, University of Thessaly, Larissa, Greece.
authors.forename: Efterpi
authors.initials: E
authors.lastname: Zafiriou
authors.affiliation: Second Department of Dermatology, School of Medicine, Aristotle University, Papageorgiou Hospital, Thessaloniki, Greece.
authors.forename: Aikaterini
authors.initials: A
authors.lastname: Patsatsi
authors.affiliation: Laboratory of Genetics, Comparative and Evolutionary Biology, Department of Biochemistry and Biotechnology, University of Thessaly, Ploutonos 26 and Aiolou, 41221, Larissa, Greece.
authors.forename: Costas
authors.initials: C
authors.lastname: Stamatis
authors.affiliation: Department of Dermatology, University General Hospital Larissa, University of Thessaly, Larissa, Greece.
authors.forename: Polyxeni
authors.initials: P
authors.lastname: Gidarokosta
authors.affiliation: Second Department of Dermatology, School of Medicine, Aristotle University, Papageorgiou Hospital, Thessaloniki, Greece.
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Sotiriadis
authors.affiliation: Laboratory of Genetics, Comparative and Evolutionary Biology, Department of Biochemistry and Biotechnology, University of Thessaly, Ploutonos 26 and Aiolou, 41221, Larissa, Greece.
authors.forename: Theologia
authors.initials: T
authors.lastname: Sarafidou
authors.affiliation: Laboratory of Genetics, Comparative and Evolutionary Biology, Department of Biochemistry and Biotechnology, University of Thessaly, Ploutonos 26 and Aiolou, 41221, Larissa, Greece. zmamur@bio.uth.gr.
authors.forename: Zissis
authors.initials: Z
authors.lastname: Mamuris
mesh_terms: D000483:Alleles; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D009154:Mutation; D056770:Netherton Syndrome / Q000175:diagnosis* / Q000235:genetics*; D010641:Phenotype; D053491:Proteinase Inhibitory Proteins, Secretory / Q000235:genetics; D000074163:Serine Peptidase Inhibitor Kazal-Type 5
chemical_list: D053491:Proteinase Inhibitory Proteins, Secretory; C120650:SPINK5 protein, human; D000074163:Serine Peptidase Inhibitor Kazal-Type 5