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

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Summary

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) (75kb, 80kb, 105kb, 110kb, 135kb, 140kb and 180kb). A total of 9/66 disease haplotypes, but only 1/61 nondisease 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.

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Author notes

  1. Maurizio Sampietro

    Present address: Institute of Molecular Medicine, John Radcliffe Hospital, Headington, Oxford, UK

Authors and Affiliations

  1. University Department of Medical Genetics, St. Mary's Hospital, M13 OJH, Manchester, UK

    Paul J. Sinnott, Rodney Harris & Tom Strachan

  2. Clinica Pediatrica, Policlinico San Matteo, I-27100, Pavia, Italy

    Chiara Livieri, Massimo Marconi & Francesca Severi

  3. Clinica Medica, Instituto Di Scienze Biomediche S.-Gerardo (Monza), Università di Milano, Milan, Italy

    Maurizio Sampietro

Authors
  1. Paul J. Sinnott
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  2. Chiara Livieri
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  3. Maurizio Sampietro
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  4. Massimo Marconi
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  5. Rodney Harris
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  6. Francesca Severi
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  7. Tom Strachan
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Sinnott, P.J., Livieri, C., Sampietro, M. et al. CYP21/C4 gene organisation in Italian 21-hydroxylase deficiency families. Hum Genet 88, 545–551 (1992). https://doi.org/10.1007/BF00219342

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  • DOI: https://doi.org/10.1007/BF00219342

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