MOLECULAR-GENETIC ANALYSIS OF PATIENTS CARRYING STEROID 21-HYDROXYLASE DEFICIENCY IN THE MEXICAN POPULATION - IDENTIFICATION OF POSSIBLE NEW MUTATIONS AND HIGH PREVALENCE OF APPARENT GERM-LINE MUTATIONS

Steroid 21-hydroxylase deficiency is the underlying cause in over 90% of patients with congenital adrenal hyperplasia, an inherited metaboli c disorder of adrenal steroidogenesis. We have characterized 94 mutant alleles from 47 unrelated Mexican patients and the corresponding muta nt alleles in their parents by amplification of the functional CYP21 g ene by PCR, followed by direct sequence analysis, The study included p atients diagnosed with the three clinical forms of the disease, Our re sults revealed: (1) the presence of relatively few mutations or combin ations of mutations associated with particular phenotypes; (2) the pre sence of putative new mutations (3) the finding of identical genotypes in patients displaying discordant phenotypes; (4) the identification of patients lacking all previous reported mutations; and (5) an appare nt high frequency of germ-line mutations, The absence of previously re ported mutations in about 22% of the disease alleles, the finding of p utative new mutations in some of the patients lacking previously known mutations, and the apparent high prevalence of germ-line mutations ma ke evident the differences in the genetic background leading to this d isorder between the Caucasian and the Mexican populations.