title: CYP21/C4 gene organisation in Italian 21-hydroxylase deficiency families.
abstract: 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.
authors.affiliation: University Department of Medical Genetics, St. Mary's Hospital, Manchester, UK.
authors.forename: P J
authors.initials: PJ
authors.lastname: Sinnott
authors.forename: C
authors.initials: C
authors.lastname: Livieri
authors.forename: M
authors.initials: M
authors.lastname: Sampietro
authors.forename: M
authors.initials: M
authors.lastname: Marconi
authors.forename: R
authors.initials: R
authors.lastname: Harris
authors.forename: F
authors.initials: F
authors.lastname: Severi
authors.forename: T
authors.initials: T
authors.lastname: Strachan
mesh_terms: D000312:Adrenal Hyperplasia, Congenital; D000483:Alleles; D015139:Blotting, Southern; D004247:DNA / Q000235:genetics / Q000302:isolation & purification; D015342:DNA Probes; D014644:Genetic Variation; D015234:HLA-A Antigens / Q000235:genetics; D015235:HLA-B Antigens / Q000235:genetics; D015236:HLA-C Antigens / Q000235:genetics; D006684:HLA-DR Antigens / Q000235:genetics; D006239:Haplotypes; D006801:Humans; D007558:Italy; D005810:Multigene Family; D009154:Mutation; D010641:Phenotype; D015183:Restriction Mapping; D013255:Steroid 21-Hydroxylase / Q000235:genetics*
chemical_list: D015342:DNA Probes; D015234:HLA-A Antigens; D015235:HLA-B Antigens; D015236:HLA-C Antigens; D006684:HLA-DR Antigens; D004247:DNA; D013255:Steroid 21-Hydroxylase