title: Evidence of postzygotic mosaicism in a transmitted form of Conradi-Hunermann-Happle syndrome associated with a novel EBP mutation.
abstract: BACKGROUND
  X-linked dominant chondrodysplasia punctata, also known as Conradi-Hünermann-Happle syndrome, is a rare skeletal dysplasia characterized by short stature, craniofacial defects, cataracts, ichthyosis, coarse hair, and alopecia. Conradi-Hünermann-Happle syndrome is caused by mutations in the gene EBP encoding Δ(8)-Δ(7) sterol isomerase emopamil-binding protein. Random X-inactivation could account for the intrafamilial variability of the phenotype of X-linked dominant chondrodysplasia punctata.
  
  
  METHODS
  We describe a girl with clinical features of X-linked dominant chondrodysplasia punctata. Biochemical analysis showed an abnormal sterol profile consistent with a defect in Δ(8)-Δ(7) sterol isomerase. Molecular studies confirmed the diagnosis by identifying a novel heterozygous missense EBP mutation (c.199C>T; p.Cys67Arg). The mutation was not detectable on genomic DNA extracted from blood lymphocytes in both parents. The mother presented with an erythematous and ichthyosiform skin lesion. EBP analysis of DNA extracted from a lesional skin biopsy revealed the presence of p.Cys67Arg mutation.
  
  
  CONCLUSIONS
  To our knowledge, we report the first molecular confirmation of postzygotic mosaicism on an ichthyosiform skin lesion in the mother of a girl with X-linked dominant chondrodysplasia punctata associated with a novel EBP mutation.
authors.affiliation: Service de Génétique Médicale, Université de Bordeaux 2, Centre Hôpitalier Universitaire de Bordeaux, Bordeaux, France. fanny.morice-picard@chu-bordeaux.fr
authors.forename: Fanny
authors.initials: F
authors.lastname: Morice-Picard
authors.forename: Elise
authors.initials: E
authors.lastname: Kostrzewa
authors.forename: Claude
authors.initials: C
authors.lastname: Wolf
authors.forename: Pascale
authors.initials: P
authors.lastname: Benlian
authors.forename: Alain
authors.initials: A
authors.lastname: Taïeb
authors.forename: Didier
authors.initials: D
authors.lastname: Lacombe
mesh_terms: D002648:Child; D002806:Chondrodysplasia Punctata / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D009030:Mosaicism; D009154:Mutation; D013251:Steroid Isomerases / Q000235:genetics*; D013261:Sterols / Q000097:blood
chemical_list: D013261:Sterols; D013251:Steroid Isomerases; C090445:EBP protein, human