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Congenital adrenal hyperplasia: focus on the molecular basis of 21-hydroxylase deficiency

Published online by Cambridge University Press:  30 April 2007

João Gonçalves ,
Ana Friães  and
Luís Moura
João Gonçalves*
Affiliation:
Centro de Genética Humana, Instituto Nacional de Saúde Dr. Ricardo Jorge, Lisboa, Portugal.
Ana Friães
Affiliation:
Previous address: Centro de Genética Humana, Instituto Nacional de Saúde Dr. Ricardo Jorge, Lisboa, Portugal. Current address: Instituto de Microbiologia, Faculdade de Medicina, Universidade de Lisboa, Lisboa, Portugal.
Luís Moura
Affiliation:
Hospital Pediátrico de Coimbra, Unidade de Endocrinologia Pediátrica, Coimbra, Portugal.
*
*Corresponding author: João Gonçalves, Sector da Patologia do Desenvolvimento Sexual, Centro de Genética Humana, Instituto Nacional de Saúde Dr. Ricardo Jorge, Av. Padre Cruz, 1649-016 Lisboa, Portugal. Tel: +351 217519320; Fax: +351 217526410; E-mail: joao.goncalves@insa.min-saude.pt
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Abstract

Congenital adrenal hyperplasia (CAH) is an autosomal recessive disorder caused by defects in one of several steroidogenic enzymes involved in the synthesis of cortisol from cholesterol in the adrenal glands. More than 90% of cases are caused by 21-hydroxylase deficiency, and the severity of the resulting clinical symptoms varies according to the level of 21-hydroxylase activity. 21-Hydroxylase deficiency is usually caused by mutations in the CYP21A2 gene, which is located on the RCCX module, a chromosomal region highly prone to genetic recombination events that can result in a wide variety of complex rearrangements, such as gene duplications, gross deletions and gene conversions of variable extensions. Molecular genotyping of CYP21A2 and the RCCX module has proved useful for a more accurate diagnosis of the disease, and prenatal diagnosis. This article summarises the clinical features of 21-hydroxylase deficiency, explains current understanding of the disease at the molecular level, and highlights recent developments, particularly in diagnosis.

Type
Research Article
Information
Expert Reviews in Molecular Medicine , Volume 9 , Issue 11 , April 2007 , pp. 1 - 23
Copyright
Copyright © Cambridge University Press 2007

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References

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Further reading, resources and contacts

CYP21A2 allele nomenclature, mutations and associated phenotypes are summarised at:

http://www.cypalleles.ki.se/cyp21.htm Google Scholar
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=OMIM Google Scholar
http://caresfoundation.org/links.htmlGoogle Scholar
http://www.genetests.org/ Google Scholar
http://www.hopkinschildrens.org/specialties/categorypages/cah Google Scholar
http://www.cahclan.org Google Scholar
http://www.hgmd.cf.ac.uk/ac/gene.php?gene=CYP21A2 Google Scholar
http://en.wikipedia.org/wiki/Congenital_adrenal_hyperplasiaGoogle Scholar