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Arch Hellen Med, 19(5), September-October 2002, 534-538


Clinical, classical and molecular genetics of 21-hydroxylase deficiency
Current concepts

2nd Department of Obstetrics and Gynecology, University of Athens, Areteion Hospital, Athens, Greece

Congenital adrenal hyperplasia due to deficiency of the enzyme 21-hydroxylase (21-OH) is divided into the classical and non-classical forms. It is one of the most common autosomal recessive inherited diseases in humans. The classical form appears at a rate of between 1:5,000 and 1:15,000 among the live neonates of North America and Europe. The rate of the non-classical form is especially high among Ashkenazi Jews and some Mediterranean populations (i.e. Italians, Hispanics). Three alleles are associated with the 21-OH locus and can combine in various ways to give rise to individuals who are either unaffected, heterozygote carriers, or affected with the classical or non-classical disease. Variable signs and symptoms of hyperandrogenemia (hirsutism, acne, virilization, short stature, menstrual irregularities) are common in both forms of the disorder. Between the genes responsible for the synthesis of the enzyme 21-OH and the antigens of the HLA system there exist both a proven genetic linkage and a proven genetic linkage disequilibrium. The most common haplotypes usually observed in the classical form are HLA-Bw47, HLAB5 and HLA-B35 and in the non-classical form of the disease the haplotype HLAB14DR1. The great progress in molecular biology during recent years has resulted in the development of new sensitive methods of DNA analysis and study, such as polymerase chain reaction and southern blot analysis. The synthesis of 21-OH is controlled by two genes, the active CYP21Β gene and the CYP21A pseudogene. All forms of the disease have known sequences of gene changes due to mutations in isolated proteins or to translocations or deletions of genetic material whole series of genes.

Key words: Congenital adrenal hyperplasia, Genetics.

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