title: Molecular diagnosis of congenital adrenal hyperplasia due to 21-hydroxylase deficiency: an update of new CYP21A2 mutations.
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.
authors.affiliation: Laboratory of Molecular Biology, Institute of Biochemistry and Clinical Biochemistry, Catholic University, Rome, Italy. paola.concolino@rm.unicatt.it
authors.forename: Paola
authors.initials: P
authors.lastname: Concolino
authors.forename: Enrica
authors.initials: E
authors.lastname: Mello
authors.forename: Cecilia
authors.initials: C
authors.lastname: Zuppi
authors.forename: Ettore
authors.initials: E
authors.lastname: Capoluongo
mesh_terms: D000312:Adrenal Hyperplasia, Congenital / Q000175:diagnosis* / Q000235:genetics; D056426:Genetic Loci; D006801:Humans; D009154:Mutation; D057089:Pathology, Molecular; D013255:Steroid 21-Hydroxylase / Q000235:genetics* / Q000378:metabolism
chemical_list: C531510:CYP21A2 protein, human; D013255:Steroid 21-Hydroxylase