title: Divergent phenotype of two siblings human leukocyte antigen identical, affected by nonclassical and classical congenital adrenal hyperplasia caused by 21-hydroxylase deficiency.
abstract: BACKGROUND
  Congenital adrenal hyperplasia (CAH) is a group of autosomal recessive disorders most often caused by enzyme 21-hydroxylase deficiency. Most mutations causing enzymatic deficiency are generated by recombinations between the active gene CYP21 and the pseudogene CYP21P. Only 1-2% of affected alleles result from spontaneous mutations. The phenotype of CAH varies greatly, usually classified as classical or nonclassical, depending on variable degree in 21-hydroxylase activity. Here we report a divergent phenotype of two human leukocyte antigen identical siblings, affected by nonclassical and classical CAH caused by 21-hydroxylase deficiency due to different genotype.
  
  
  METHODS
  Using direct sequencing method and Southern blot, we studied two children (one male and one female), affected, respectively, by nonclassical and classical CAH and their parents.
  
  
  RESULTS
  The mother was heterozygous for the Q318X mutation, and the father was heterozygous for the V281L mutation. The brother was a compound heterozygote for the mutations V281L and Q318X, whereas the proband was compound heterozygote for the Q318X mutation and a large conversion. The two children are human leukocyte antigen identical (A*02;B*14;DRB1*01/A*33;B*14;DRB1*03).
  
  
  CONCLUSIONS
  Different phenotype of the proband is the result of compound heterozygosity for the maternal mutation Q318X and a de novo large conversion.
authors.affiliation: Department of Internal Medicine, University of Rome Tor Vergata, Via di Montpellier 1, 00133 Rome, Italy. porzio@uniroma2.it
authors.forename: O
authors.initials: O
authors.lastname: Porzio
authors.forename: V
authors.initials: V
authors.lastname: Cunsolo
authors.forename: M
authors.initials: M
authors.lastname: Malaponti
authors.forename: E
authors.initials: E
authors.lastname: De Nisco
authors.forename: A
authors.initials: A
authors.lastname: Acquafredda
authors.forename: L
authors.initials: L
authors.lastname: Cavallo
authors.forename: M
authors.initials: M
authors.lastname: Andreani
authors.forename: E
authors.initials: E
authors.lastname: Giardina
authors.forename: M
authors.initials: M
authors.lastname: Testi
authors.forename: M
authors.initials: M
authors.lastname: Cappa
authors.forename: G
authors.initials: G
authors.lastname: Federici
mesh_terms: D000312:Adrenal Hyperplasia, Congenital / Q000235:genetics*; D002648:Child; D002869:Chromosome Aberrations; D005260:Female; D015321:Gene Rearrangement; D006680:HLA Antigens / Q000032:analysis*; D006650:Histocompatibility Testing; D006801:Humans; D008297:Male; D010641:Phenotype; D017354:Point Mutation; D012150:Polymorphism, Restriction Fragment Length; D035781:Siblings; D013255:Steroid 21-Hydroxylase / Q000235:genetics*
chemical_list: D006680:HLA Antigens; D013255:Steroid 21-Hydroxylase