title: Association of p.His38Leu, a rare CYP21A2 mutation, with the classical simple virilizing phenotype of 21-hydroxylase deficiency in a 6-year-old boy.
abstract: OBJECTIVE
  Congenital adrenal hyperplasia due to 21-hydroxylase deficiency is one of the most common autosomal recessive disorders. Unequal crossing over or gene conversion between the active CYP21A2 gene and the inactive CYP21A1P pseudogene accounts for 95% of mutations, but many non-pseudogene-derived mutations have been described. It is important for these new mutations to be assigned to a specific phenotype.
  
  
  RESULTS
  We report a young boy diagnosed with the classical simple virilizing phenotype in whom the CYP21A2 genetic analysis disclosed that he was a compound heterozygous for p.His38Leu and the c.290-13A/C>G mutations. The p.His38Leu mutation has been recently described, but has not been associated with a specific phenotype thus far. Residue 38 is the only charged amino acid of a hydrophobic patch that interacts closely with the membrane. This mutation leads to a non-charged amino acid, suggesting a much more hydrophobic continuous domain. This patch is highly conserved through different mammals indicating the importance of this domain in the protein-membrane interaction.
  
  
  CONCLUSIONS
  Our results support p.His38Leu as a severe mutation causing a classical simple virilizing phenotype.
authors.affiliation: Biochemistry and Molecular Genetics Department, CDB, Hospital Clínic, Barcelona, Spain. joriola@clinic.ub.es
authors.forename: Josep
authors.initials: J
authors.lastname: Oriola
authors.forename: Maria Zelmira
authors.initials: MZ
authors.lastname: Bosch
authors.forename: Carme
authors.initials: C
authors.lastname: Valls
authors.forename: Lourdes
authors.initials: L
authors.lastname: Ibáñez
mesh_terms: D000312:Adrenal Hyperplasia, Congenital / Q000175:diagnosis / Q000235:genetics*; D001483:Base Sequence; D002648:Child; D005260:Female; D056726:Genetic Association Studies; D006639:Histidine / Q000235:genetics; D006801:Humans; D007930:Leucine / Q000235:genetics; D008297:Male; D059645:Mutation Rate; D020125:Mutation, Missense; D010375:Pedigree; D010641:Phenotype; D013255:Steroid 21-Hydroxylase / Q000235:genetics*; D014770:Virilism / Q000235:genetics*
chemical_list: D006639:Histidine; C531510:CYP21A2 protein, human; D013255:Steroid 21-Hydroxylase; D007930:Leucine