Pro-453 to Ser mutation in CYP21 is associated with nonclassic steroid 21-hydroxylase deficiency

• Published in: Molecular endocrinology (Baltimore, Md.) Vol. 6; no. 8; p. 1211
• Main Authors: Owerbach, D, Sherman, L, Ballard, A L, Azziz, R
• Format: Journal Article
• Language: English
• Published: United States 01-08-1992
• Subjects: Adrenal Hyperplasia, Congenital - genetics; Base Sequence; DNA - genetics; Female; Humans; Molecular Sequence Data; Point Mutation; Proline - genetics; Serine - genetics
• ISSN: 0888-8809
• DOI: 10.1210/me.6.8.1211

Steroid 21-hydroxylase deficiency is the leading cause of impaired cortisol synthesis in congenital adrenal hyperplasia (CAH), with the nonclassic form (NC) comprising approximately 1% of the Caucasian population. The structure of the CYP21 gene was studied in 13 unrelated NC-CAH patients, three affected siblings, and 55 blood donors using polymerase chain reaction. In addition to the Leu-281 and Leu-30 mutations previously associated with NC-CAH, the finding of a Pro-453 to Ser mutation in exon-10 of CYP21 in the NC-CAH patients is reported. Ser-453 was found in 46.2% of unrelated NC-CAH patients, but only 7.7% and 3.6% of salt-wasting CAH patients and blood donors, respectively. In contrast to the Leu-281 and Leu-30 mutations, Ser-453 has not been previously detected in the CYP21 pseudogene (CYP21P) and, therefore, has not likely arisen by gene conversion.