title: A novel mutation in the connexin 26 gene (GJB2) in a child with clinical and histological features of keratitis-ichthyosis-deafness (KID) syndrome.
abstract: BACKGROUND
  Keratitis-ichthyosis-deafness (KID) syndrome is a rare congenital ectodermal disorder, caused by heterozygous missense mutation in GJB2, encoding the gap junction protein connexin 26. The commonest mutation is the p.Asp50Asn mutation, and only a few other mutations have been described to date.
  
  
  OBJECTIVE
  To report the fatal clinical course and characterize the genetic background of a premature male neonate with the clinical and histological features of KID syndrome.
  
  
  METHODS
  Genomic DNA was extracted from peripheral blood and used for PCR amplification of the GJB2 gene. Direct sequencing was used for mutation analysis.
  
  
  RESULTS
  The clinical features included hearing impairment, ichthyosiform erythroderma with hyperkeratotic plaques, palmoplantar keratoderma, alopecia of the scalp and eyelashes, and a thick vernix caseosa-like covering of the scalp. On histological analysis, features characteristic of KID syndrome, such as acanthosis and papillomatosis of the epidermis with basket-weave hyperkeratosis, were seen. The skin symptoms were treated successfully with acitretin 0.5 mg/kg. The boy developed intraventricular and intracerebral haemorrhage, leading to hydrocephalus. His condition was further complicated by septicaemia and meningitis caused by infection with extended-spectrum beta-lactamase-producing Klebsiella pneumoniae. Severe respiratory failure followed, and the child died at 46 weeks of gestational age (13 weeks postnatally). Sequencing of the GJB2 gene showed that the child was heterozygous for a novel nucleotide change, c.263C>T, in exon 2, leading to a substitution of alanine for valine at position 88 (p.Ala88Val).
  
  
  CONCLUSIONS
  This study has identified a new heterozygous de novo mutation in the Cx26 gene (c.263C>T; p.Ala88Val) leading to KID syndrome.
authors.affiliation: Department of Dermatology, Aarhus University Hospital, Aarhus, Denmark. uffkop@rm.dk
authors.forename: U
authors.initials: U
authors.lastname: Koppelhus
authors.forename: L
authors.initials: L
authors.lastname: Tranebjaerg
authors.forename: G
authors.initials: G
authors.lastname: Esberg
authors.forename: M
authors.initials: M
authors.lastname: Ramsing
authors.forename: M
authors.initials: M
authors.lastname: Lodahl
authors.forename: N D
authors.initials: ND
authors.lastname: Rendtorff
authors.forename: H V
authors.initials: HV
authors.lastname: Olesen
authors.forename: M
authors.initials: M
authors.lastname: Sommerlund
mesh_terms: D000818:Animals; D001706:Biopsy; D000072259:Connexin 26; D017630:Connexins / Q000235:genetics*; D003638:Deafness / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D003879:Dermatologic Agents / Q000627:therapeutic use; D017809:Fatal Outcome; D006801:Humans; D007057:Ichthyosis / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D007231:Infant, Newborn; D007234:Infant, Premature; D007235:Infant, Premature, Diseases / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D007634:Keratitis / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D008297:Male; D009154:Mutation; D012867:Skin / Q000473:pathology
chemical_list: D017630:Connexins; D003879:Dermatologic Agents; C000607042:GJB2 protein, human; D000072259:Connexin 26