title: Prenatal testing for a novel EBP missense mutation causing X-linked dominant chondrodysplasia punctata.
abstract: OBJECTIVE
  To determine the pathogenicity of a novel conserved missense mutation, p.Ser98Phe, in the emopamil binding protein (EBP) gene in order to perform a prenatal diagnostic test for X-linked dominant chondrodysplasia punctata (CDPX2) in a male foetus at 50% risk.
  
  
  METHODS
  Family members were tested for p.Ser98Phe using PCR and sequence analysis of leucocyte or buccal cell DNA. Haplotype analysis was employed to identify the grandparental chromosome on which p.Ser98Phe had arisen. In silico protein analyses were used to predict whether p.Ser98Phe significantly altered the EBP protein structure.
  
  
  RESULTS
  The mutation was detected in the proband and her affected mother but not in the maternal grandmother, who was thought to be mildly affected. However, haplotype analysis showed that p.Ser98Phe had arisen de novo on the grandpaternal X chromosome. Protein secondary structure predictions suggested that p.Ser98Phe alters the properties of the helix within which it is located.
  
  
  CONCLUSIONS
  We concluded that p.Ser98Phe is likely to be pathogenic and proceeded with prenatal testing. The male foetus had not inherited p.Ser98Phe and his unaffected status was confirmed at birth. This family demonstrates some of the difficulties in interpreting the significance of novel missense mutations, particularly when results are needed urgently for prenatal diagnosis.
authors.affiliation: Department of Molecular Genetics, Royal Devon & Exeter NHS Foundation Trust, Exeter, UK.
authors.forename: Carolyn
authors.initials: C
authors.lastname: Tysoe
authors.forename: Caroline J
authors.initials: CJ
authors.lastname: Law
authors.forename: Richard
authors.initials: R
authors.lastname: Caswell
authors.forename: Peter
authors.initials: P
authors.lastname: Clayton
authors.forename: Sian
authors.initials: S
authors.lastname: Ellard
mesh_terms: D002806:Chondrodysplasia Punctata / Q000175:diagnosis / Q000235:genetics*; D005260:Female; D005817:Genetic Counseling; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D020125:Mutation, Missense; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011247:Pregnancy; D011296:Prenatal Diagnosis; D013251:Steroid Isomerases / Q000235:genetics*
chemical_list: D013251:Steroid Isomerases; C090445:EBP protein, human