title: Netherton syndrome in two Japanese siblings with a novel mutation in the SPINK5 gene: immunohistochemical studies of LEKTI and other epidermal molecules.
abstract: BACKGROUND
  Netherton syndrome (NS) is a severe autosomal recessive disorder characterized by ichthyosiform erythroderma, bamboo hair and atopy. The disease is caused by mutations in the SPINK5 gene, which encodes a putative serine protease inhibitor, LEKTI (lymphoepithelial Kazal-type-related inhibitor). Previous studies have clearly shown a crucial role for LEKTI in skin barrier formation.
  
  
  OBJECTIVE
  To identify pathogenic mutations in two Japanese siblings with NS, and further to investigate the consequences of the mutations at the protein level.
  
  
  METHODS
  To screen for mutations in the SPINK5 gene, all of its exons and splice junctions were amplified by polymerase chain reaction and directly sequenced. In addition, immunohistochemical staining of LEKTI, desmoglein (Dsg) 1 and elafin was performed with their specific antibodies.
  
  
  RESULTS
  Mutation analysis resulted in the identification of compound heterozygous mutations, Q713X and R790X, in the SPINK5 gene of both patients. The former one is a novel mutation. Immunohistochemical studies in one patient demonstrated a complete absence of LEKTI and a strong expression of elafin in the patient's skin. Dsg1 was normally expressed in our patient.
  
  
  CONCLUSIONS
  In this report, we describe compound heterozygous mutations in the SPINK5 gene in two Japanese siblings with NS. The result of immunohistochemistry shows LEKTI deficiency and upregulation of elafin in the skin of one patient. Furthermore, our data indicate that degradation of Dsg1 does not always occur in NS.
authors.affiliation: Department of Dermatology, Niigata University School of Medicine, Asahimachi-dori, Niigata 951-8510, Japan. yshimo@med.niigata-u.ac.jp
authors.forename: Y
authors.initials: Y
authors.lastname: Shimomura
authors.forename: N
authors.initials: N
authors.lastname: Sato
authors.forename: N
authors.initials: N
authors.lastname: Kariya
authors.forename: S
authors.initials: S
authors.lastname: Takatsuka
authors.forename: M
authors.initials: M
authors.lastname: Ito
mesh_terms: D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism*; D002675:Child, Preschool; D004817:Epidermis / Q000378:metabolism; D006197:Hair / Q000002:abnormalities; D006801:Humans; D016113:Ichthyosiform Erythroderma, Congenital / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D007223:Infant; D008297:Male; D009154:Mutation; D010375:Pedigree; D053491:Proteinase Inhibitory Proteins, Secretory; D000074163:Serine Peptidase Inhibitor Kazal-Type 5; D013577:Syndrome
chemical_list: D002352:Carrier Proteins; D053491:Proteinase Inhibitory Proteins, Secretory; C120650:SPINK5 protein, human; D000074163:Serine Peptidase Inhibitor Kazal-Type 5