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

• Published in: Human genetics Vol. 102; no. 2; pp. 170 - 177
• Main Authors: ORDONEZ-SANCHEZ, M. L, RAMIREZ-JIMENEZ, S, TUSIE-LUNA, M. T, LOPEZ-GUTIERREZ, A. U, RIBA, L, GAMBOA-CARDIEL, S, CERRILLO-HINOJOSA, M, ALTAMIRANO-BUSTAMANTE, N, CALZADA-LEON, R, ROBLES-VALDES, C, MENDOZA-MORFIN, F
• Format: Journal Article
• Language: English
• Published: Heidelberg Springer 01.02.1998; Berlin; New York, NY
• Subjects: Adrenal Hyperplasia, Congenital - enzymology; Adrenal Hyperplasia, Congenital - epidemiology; Adrenal Hyperplasia, Congenital - genetics; Adrenals. Adrenal axis. Renin-angiotensin system (diseases); Biological and medical sciences; CYP21 gene; DNA Mutational Analysis; Endocrinopathies; Female; Genetic Testing; Genotype; Germ-Line Mutation; Humans; Male; Malignant tumors; Medical sciences; Mexico - epidemiology; Point Mutation; Polymerase Chain Reaction; Prevalence; Sequence Analysis, DNA; steroid 21-hydroxylase; Steroid 21-Hydroxylase - genetics; Central America; Mexico; America; Endocrinopathy; Human; Prevalence; Adrenal cortex diseases; Enzyme; Deficiency; Hyperadrenocorticism; Enzymopathy; Genetic disease; Congenital adrenal hyperplasia syndrome; Gene; Adrenal gland diseases; Steroidogenesis; Oxidoreductases; Mutation; Steroid 21-monooxygenase
• ISSN: 0340-6717; 1432-1203
• DOI: 10.1007/s004390050672

Steroid 21-hydroxylase deficiency is the underlying cause in over 90% of patients with congenital adrenal hyperplasia, an inherited metabolic disorder of adrenal steroidogenesis. We have characterized 94 mutant alleles from 47 unrelated Mexican patients and the corresponding mutant alleles in their parents by amplification of the functional CYP21 gene by PCR, followed by direct sequence analysis. The study included patients diagnosed with the three clinical forms of the disease. Our results revealed: (1) the presence of relatively few mutations or combinations of mutations associated with particular phenotypes; (2) the presence 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 apparent high frequency of germ-line mutations. The absence of previously reported mutations in about 22% of the disease alleles, the finding of putative new mutations in some of the patients lacking previously known mutations, and the apparent high prevalence of germ-line mutations make evident the differences in the genetic background leading to this disorder between the Caucasian and the Mexican populations.