title: Netherton syndrome with extensive skin peeling and failure to thrive due to a homozygous frameshift mutation in SPINK5.
abstract: BACKGROUND
  Netherton syndrome (NTS) is a rare autosomal recessive multisystem disorder characterized by congenital erythroderma and ichthyosis, hair shaft abnormalities and immune dysregulation. The disorder is caused by deleterious mutations in the SPINK5 gene, encoding the serine protease inhibitor LEKTI.
  
  
  OBJECTIVE
  Our objective was to investigate if the erythrodermic variant of peeling skin syndrome is also caused by SPINK5 mutations and to study the consequences of the disease on infantile brain development.
  
  
  METHODS
  In an infant with extensive erythroderma, peeling skin and failure to thrive, we analyzed the SPINK5 gene for pathogenic mutations by direct DNA sequencing and performed repeated brain MRI studies with diffusion-weighted imaging.
  
  
  RESULTS
  We identified a homozygous 4-base-pair insertion in exon 5 of SPINK5, which introduces a premature termination codon and appears to be a common mutation among West Indies islanders. MRI analyses revealed a persistent diffuse volume loss.
  
  
  CONCLUSIONS
  Our results confirm that early truncation mutations of the coding sequence of SPINK5 produce a severe phenotype and that generalized peeling skin is one of the manifestations of NTS. We further demonstrate for the first time that NTS may be associated with MRI abnormalities indicative of a permanent tissue injury of the brain.
authors.affiliation: Department of Dermatology, Columbia University Medical Center, Columbia University, New York, NY, USA.
authors.forename: Adam S
authors.initials: AS
authors.lastname: Geyer
authors.forename: Paulina
authors.initials: P
authors.lastname: Ratajczak
authors.forename: Marlyanne
authors.initials: M
authors.lastname: Pol-Rodriguez
authors.forename: William S
authors.initials: WS
authors.lastname: Millar
authors.forename: Maria
authors.initials: M
authors.lastname: Garzon
authors.forename: Gabriele
authors.initials: G
authors.lastname: Richard
mesh_terms: D001707:Biopsy, Needle; D004252:DNA Mutational Analysis; D005183:Failure to Thrive / Q000175:diagnosis / Q000235:genetics; D005500:Follow-Up Studies; D016368:Frameshift Mutation; D020022:Genetic Predisposition to Disease; D006201:Hair Diseases / Q000235:genetics* / Q000473:pathology; D006801:Humans; D016113:Ichthyosiform Erythroderma, Congenital / Q000235:genetics* / Q000473:pathology; D007150:Immunohistochemistry; D007223:Infant; D008279:Magnetic Resonance Imaging; D008297:Male; D016133:Polymerase Chain Reaction; D015842:Serine Proteinase Inhibitors / Q000235:genetics*; D012720:Severity of Illness Index; D013577:Syndrome
chemical_list: D015842:Serine Proteinase Inhibitors