CYP21/C4 gene organisation in Italian 21-hydroxylase deficiency families

Hum Genet. 1992 Mar;88(5):545-51. doi: 10.1007/BF00219342.


A total of 33 Italian 21-hydroxylase (21-OH) deficiency families were investigated using a combination of short and long range restriction mapping of the CYP21/C4 gene cluster. The analyses revealed that large-scale length polymorphism in this gene cluster strictly conformed to a compound variable number of tandem repeats (VNTR) plus insertion system with between one and four CYP21 + C4 units and seven BssHII restriction fragment length polymorphisms (RFLPs) (75 kb, 80 kb, 105 kb, 110 kb, 135 kb, 140 kb and 180 kb). A total of 9/66 disease haplotypes, but only 1/61 non-disease haplotypes, showed evidence of gene addition by exhibiting three or more CYP21 + C4 repeat units. Of these, two were identified in one 21-OH deficiency patient who has a total of eight CYP21 + C4 units, being homozygous for the HLA haplotype DR2 DQ2 B5 A28. This haplotype carries four CYP21 + C4 units, three of which contain CYP21A-like genes and one of which contains a CYP21B-like gene that presumably carries a pathological point mutation. Of the other gene addition haplotypes associated with 21-OH deficiency, four show three CYP21 + C4 units flanked by HLA-DR1 and HLA-B14 markers. Although such haplotypes have commonly been associated with non-classical 21-OH deficiency, three examples in the present study are unexpectedly found in two salt-wasting patients, who are respectively homozygous or heterozygous for this haplotype. Only 7/66 disease haplotypes showed evidence of a CYP21B gene deletion.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenal Hyperplasia, Congenital*
  • Alleles
  • Blotting, Southern
  • DNA / genetics
  • DNA / isolation & purification
  • DNA Probes
  • Genetic Variation
  • HLA-A Antigens / genetics
  • HLA-B Antigens / genetics
  • HLA-C Antigens / genetics
  • HLA-DR Antigens / genetics
  • Haplotypes
  • Humans
  • Italy
  • Multigene Family*
  • Mutation*
  • Phenotype
  • Restriction Mapping
  • Steroid 21-Hydroxylase / genetics*


  • DNA Probes
  • HLA-A Antigens
  • HLA-B Antigens
  • HLA-C Antigens
  • HLA-DR Antigens
  • DNA
  • Steroid 21-Hydroxylase