Pro-453 to Ser mutation in CYP21 is associated with nonclassic steroid 21-hydroxylase deficiency.
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.
Owerbach
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D
Department of Pediatrics, Baylor College of Medicine, Houston, Texas 77030.
Sherman
L
L
Ballard
A L
AL
Azziz
R
R
D000312:Adrenal Hyperplasia, Congenital / Q000235:genetics*; D001483:Base Sequence; D004247:DNA / Q000235:genetics; D005260:Female; D006801:Humans; D008969:Molecular Sequence Data; D017354:Point Mutation; D011392:Proline / Q000235:genetics*; D012694:Serine / Q000235:genetics*
D012694:Serine; D004247:DNA; D011392:Proline