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Novel mutations in the human CYP21 gene
1Department of Tissue Typing, Finnish Red Cross Blood Transfusion Service, Kivihaantie 7, FIN-00310 Helsinki, Finland. antti.levo@helsinki.fi
Abstract:
The great majority of genetic defects underlying steroid 21-hydroxylase deficiency appear to result from intergenic recombinations between the homologous CYP21 and CYP21P genes. For a minority, novel sporadic point mutations have been detected. De novo mutations in CYP21 have also been reported, but only a few studies have systematically screened their occurrence. We here describe a population-based patient sample in order to estimate the rate of single-family (i.e. sporadic) and de novo germline mutations in the human CYP21 locus. Among 76 Finnish families were observed three single-family mutations and two de novo mutations in CYP21. The rates obtained, approximately 5% and approximately 2% for novel and de novo mutations, respectively, indicate that they are not rare and that their occurrence should not be ignored in genetic diagnostics of this disorder.
Insights
Genetic defects in steroid 21-hydroxylase deficiency are often caused by gene recombination. Novel and de novo mutations in the CYP21 gene are more common than previously thought, impacting genetic diagnostics.
Area of Science:
- Genetics
- Molecular Biology
- Endocrinology
Background:
- Steroid 21-hydroxylase deficiency is a genetic disorder.
- Most cases are linked to intergenic recombination between CYP21 and CYP21P genes.
- The frequency of novel sporadic and de novo mutations in CYP21 is not well-established.
Purpose of the Study:
- To estimate the occurrence rate of single-family (sporadic) and de novo germline mutations in the CYP21 gene.
- To assess the significance of these mutations in the genetic diagnostics of steroid 21-hydroxylase deficiency.
Main Methods:
- Analysis of a population-based sample of 76 Finnish families.
- Systematic screening for mutations in the CYP21 locus.
Main Results:
- Three single-family mutations and two de novo mutations were identified in CYP21 among the 76 families.
- The estimated rates were approximately 5% for novel mutations and approximately 2% for de novo mutations.
Conclusions:
- Novel and de novo mutations in CYP21 are not rare.
- These mutations should be considered in the genetic diagnostics of steroid 21-hydroxylase deficiency.