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

Abstract

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.

Mutation Analysis in Patients with Congenital Adrenal Hyperplasia in the Spanish Population: Identification of Putative Novel Steroid 21-Hydroxylase Deficiency Alleles Associated with the Classic Form of the Disease

“…Among them, only the P453S was detected in our sample at a frequency of 9.2%, which is very close to the 7.7% observed by Owerbach et al [33]. The high frequency of this mutation favored the idea that it is not sporadic and that it might constitute a polymorphism of the pseudogene that had been transferred to the CYP21 gene by gene conversion [11, 26].…”

“…In general, we found no significant differences in the frequency of the mutations in our sample compared with previous studies [22, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39]. …”

Classical and nonclassical 21‐hydroxylase deficiency: a molecular study of Argentine patients

“…Nevertheless, the possibility that the number of patients analysed in the present sample accounts for the differences observed cannot be excluded. On the other hand, although a frequency close to 20% was reported for P453S among NC patients in Texas (Owerbach et al , 1992b), this mutation represents only the 2·3% of the NC alleles in our cohort. The same frequency was found in Brazil (Bachega et al , 1998) and a frequency of 5% was reported in a recent study from Italy (Balsamo et al , 2000), being the only available data regarding the frequency of this mutation in the NC patients from Latin populations.…”

Genotype‐phenotype analysis in late onset 21‐hydroxylase deficiency in comparison to the classical forms

“…Two novel mutations, R339H and P453S, which in vitro cause a 50% reduction of normal CYP21 activity (Helmberg et al 1992) have been found in a LOCAH patient of Turkish descent. One of these mutations, P453S was subsequently found in 46% of unrelated LOCAH patients in a study from the USA (Owerbach et al 1992). Neither of these mutations were found in our patient group.…”