title: Clinical, molecular and biochemical characterization of nine Spanish families with Conradi-Hünermann-Happle syndrome: new insights into X-linked dominant chondrodysplasia punctata with a comprehensive review of the literature.
abstract: BACKGROUND
  Conradi-Hünermann-Happle syndrome (CDPX2, OMIM 302960) is an inherited X-linked dominant variant of chondrodysplasia punctata which primarily affects the skin, bones and eyes. CDPX2 results from mutations in EBP (emopamil binding protein), and presents with increased levels of sterol precursors 8(9)-cholesterol and 8-dehydrocholesterol.
  
  
  OBJECTIVE
  To expand the understanding of CDPX2, clinically, biochemically and genetically.
  
  
  METHODS
  We present one of the largest series reported to date, including 13 female patients belonging to nine Spanish families. Patients were studied biochemically using gas chromatography-mass spectrometry, genetically using polymerase chain reaction and in their methylation status using the HUMARA assay.
  
  
  RESULTS
  In our cases, there was a clear relationship between abnormal sterol profile and the EBP gene mutation. We describe three novel mutations in the EBP gene. EBP mutations were inherited in three out of nine families and were sporadic in the remaining cases.
  
  
  CONCLUSIONS
  No clear genotype-phenotype correlation was found. Patients' biochemical profiles did not reveal a relationship between sterol profiles and severity of disease. A skewed X-chromosome inactivation may explain the clinical phenotype in CDPX2 in some familial cases.
authors: Department of Dermatology, University Hospital of Salamanca, Salamanca, Spain. jcanueto@yahoo.es
authors: J
authors: J
authors: Cañueto
authors: M
authors: M
authors: Girós
authors: S
authors: S
authors: Ciria
authors: G
authors: G
authors: Pi-Castán
authors: M
authors: M
authors: Artigas
authors: J
authors: J
authors: García-Dorado
authors: V
authors: V
authors: García-Patos
authors: A
authors: A
authors: Virós
authors: T
authors: T
authors: Vendrell
authors: A
authors: A
authors: Torrelo
authors: A
authors: A
authors: Hernández-Martín
authors: E
authors: E
authors: Martín-Hernández
authors: M T
authors: MT
authors: Garcia-Silva
authors: M
authors: M
authors: Fernández-Burriel
authors: J
authors: J
authors: Rosell
authors: M
authors: M
authors: Tejedor
authors: F
authors: F
authors: Martínez
authors: J
authors: J
authors: Valero
authors: J L
authors: JL
authors: García
authors: E M
authors: EM
authors: Sánchez-Tapia
authors: P
authors: P
authors: Unamuno
authors: R
authors: R
authors: González-Sarmiento
mesh_terms: D000328:Adult; D002775:Cholestadienols / Q000378:metabolism; D002784:Cholesterol / Q000378:metabolism; D002806:Chondrodysplasia Punctata / Q000235:genetics* / Q000378:metabolism; D004252:DNA Mutational Analysis / Q000379:methods; D005260:Female; D040181:Genetic Diseases, X-Linked / Q000235:genetics* / Q000378:metabolism; D005838:Genotype; D006801:Humans; D007223:Infant; D009154:Mutation / Q000235:genetics*; D010641:Phenotype; D013030:Spain; D013251:Steroid Isomerases / Q000235:genetics*; D049951:X Chromosome Inactivation / Q000235:genetics*
chemical_list: D002775:Cholestadienols; C026359:cholesta-5,8-dien-3 beta-ol; D002784:Cholesterol; D013251:Steroid Isomerases; C090445:EBP protein, human; C056855:zymostenol