1. Molecular diagnosis of congenital adrenal hyperplasia due to 21-hydroxylase deficiency: an update of new CYP21A2 mutations
- Author
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Cecilia Zuppi, Ettore Capoluongo, Enrica Mello, Paola Concolino, Concolino, P, Mello, E, Zuppi, C, and Capoluongo, E
- Subjects
medicine.medical_specialty ,Steroid 21-Hydroxylase ,Pseudogene ,Clinical Biochemistry ,Biology ,urologic and male genital diseases ,medicine.disease_cause ,Congenital adrenal hyperplasia due to 21-hydroxylase deficiency ,Internal medicine ,medicine ,Humans ,Congenital adrenal hyperplasia ,Pathology, Molecular ,Allele ,Gene ,Genetics ,Mutation ,Adrenal Hyperplasia, Congenital ,Biochemistry (medical) ,Metabolic disorder ,General Medicine ,medicine.disease ,Endocrinology ,Genetic Loci - Abstract
Steroid 21-hydroxylase deficiency is present in more than 90% of patients with congenital adrenal hyperplasia, an inherited metabolic disorder of adrenal steroidogenesis. Impaired enzymatic activity leads to the accumulation of metabolic intermediates (progesterone and 17-hydroxyprogesterone), which results in excessive androgen production and varied signs of virilisation. CYP21A2 is an active gene and encodes for the steroid 21-hydroxylase enzyme, whereas CYP21A1P is an inactive pseudogene that contains a series of deleterious mutations. The major part of disease-causing mutations in CYP21A2 alleles are CYP21A1P-derived sequence transferred to the active gene by macro or microconversion events. Approximately 5% of all disease-causing CYP21A2 alleles harbour rare mutations that do not originate from the pseudogene. A list of all reported CYP21A2 mutations can be found in the CYP21A2 database created by the Human Cytochrome P450 (CYP) Allele Nomenclature Committee (http:www.imm.Ki.se/CYPalleles/cyp21.htm). Unfortunately, the last update of this database was in 2006. However, over the last 4 years many other novel CYP21A2 mutations have been reported in PubMed. The aim of this review is to provide a focus on the molecular and genetic aspects of the diagnosis of 21-hydroxylase deficiency. In addition, an updated list of the last new CYP21A2 mutations is included. Clin Chem Lab Med 2010;48:1057–62.
- Published
- 2010