title: EEC (Ectrodactyly, Ectodermal dysplasia, Clefting) syndrome: heterozygous mutation in the p63 gene (R279H) and DNA-based prenatal diagnosis.
abstract: BACKGROUND
  Germline mis-sense mutations in the DNA-binding domain of the p63 gene have recently been established as the molecular basis for the autosomal dominant EEC (Ectrodactyly, Ectodermal dysplasia, Clefting) syndrome.
  
  
  OBJECTIVE
  To examine genomic DNA from a 36-year-old woman, her 58-year-old father and her 11-year-old son, all with the EEC syndrome, to determine the inherent p63 mutation and, after genetic counselling, to use knowledge of the mutation to undertake a first-trimester DNA-based prenatal diagnosis in a subsequent pregnancy.
  
  
  METHODS
  Fetal DNA was extracted from chorionic villi and used to amplify exon 7 of p63 containing the potential mutation. Direct sequencing and restriction endonuclease digestion (loss of AciI site on mutant allele) were used for DNA-based prenatal diagnosis.
  
  
  RESULTS
  We identified a heterozygous arginine to histidine p63 mutation, R279H, in all three affected individuals. Prenatal diagnosis demonstrated a homozygous wild-type sequence predicting an unaffected child: a healthy boy was subsequently born at full-term.
  
  
  CONCLUSIONS
  These data expand the p63 gene mutation database and provide the first example of a DNA-based prenatal test in this ectodermal dysplasia syndrome.
authors.affiliation: Department of Cell and Molecular Pathology, St John's Institute of Dermatology, The Guy's, King's College and St Thomas' Hospitals' Medical School, St Thomas' Hospital, Lambeth Palace Road, London SE1 7EH, UK.
authors.forename: A P
authors.initials: AP
authors.lastname: South
authors.forename: G H S
authors.initials: GH
authors.lastname: Ashton
authors.forename: C
authors.initials: C
authors.lastname: Willoughby
authors.forename: I H
authors.initials: IH
authors.lastname: Ellis
authors.forename: O
authors.initials: O
authors.lastname: Bleck
authors.forename: T
authors.initials: T
authors.lastname: Hamada
authors.forename: G
authors.initials: G
authors.lastname: Mannion
authors.forename: V
authors.initials: V
authors.lastname: Wessagowit
authors.forename: T
authors.initials: T
authors.lastname: Hashimoto
authors.forename: R A J
authors.initials: RA
authors.lastname: Eady
authors.forename: J A
authors.initials: JA
authors.lastname: McGrath
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics; D000328:Adult; D002648:Child; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins; D004476:Ectodermal Dysplasia / Q000235:genetics*; D005260:Female; D016147:Genes, Tumor Suppressor; D005820:Genetic Testing / Q000379:methods; D018095:Germ-Line Mutation; D006801:Humans; D008297:Male; D008565:Membrane Proteins; D008875:Middle Aged; D020125:Mutation, Missense; D010375:Pedigree; D010750:Phosphoproteins / Q000235:genetics*; D011296:Prenatal Diagnosis / Q000379:methods*; D013577:Syndrome; D014034:Toes / Q000002:abnormalities; D015534:Trans-Activators / Q000235:genetics*; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins
chemical_list: C081876:CKAP4 protein, human; D004268:DNA-Binding Proteins; D008565:Membrane Proteins; D010750:Phosphoproteins; C115051:TP63 protein, human; D015534:Trans-Activators; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins