CYP21 mutations in Brazilian patients with 21-hydroxylase deficiency

• Published in: Human genetics Vol. 106; no. 4; pp. 414 - 419
• Main Authors: WITCHEL, S. F, SMITH, R, CRIVELLARO, C. E, DELLA MANNA, T, DICHTCHEKENIAN, V, SETIAN, N, DAMIANI, D
• Format: Journal Article
• Language: English
• Published: Heidelberg Springer 01-04-2000; Berlin; New York, NY
• Subjects: Adrenal Hyperplasia, Congenital - genetics; Adrenals. Adrenal axis. Renin-angiotensin system (diseases); Age of Onset; Alleles; Biological and medical sciences; Brazil; Child; Child, Preschool; Classical genetics, quantitative genetics, hybrids; Endocrinopathies; Female; Fundamental and applied biological sciences. Psychology; Genetics of eukaryotes. Biological and molecular evolution; Genotype; Human; Humans; Infant; Infant, Newborn; Male; Malignant tumors; Medical sciences; Mutation; Phenotype; Steroid 21-Hydroxylase - genetics; South America; Brazil; America; Endocrinopathy; Human; Adrenal cortex diseases; Enzyme; Family study; Deficiency; Genotype; Hyperadrenocorticism; Enzymopathy; Case study; Congenital adrenal hyperplasia syndrome; Adrenal gland diseases; Oxidoreductases; Mutation; Steroid 21-monooxygenase
• ISSN: 0340-6717; 1432-1203
• DOI: 10.1007/s004390000276

Congenital adrenal hyperplasia caused by 21-hydroxylase deficiency is a common autosomal recessive disorder resulting from mutations in the 21-hydroxylase (CYP21) gene. To develop a strategy to screen for the most commonly occurring CYP21 mutations in Brazil, we performed molecular genotype analysis on 73 children with CAH representing 71 unrelated families. The techniques used for CYP21 molecular genotype analysis were: restriction fragment length polymorphism, single-strand conformational polymorphism, allele-specific oligonucleotide hybridization, allele-specific polymerase chain reaction amplification, and heteroduplex analyses. Mutations were identified on all but eight affected alleles. The intron 2 splicing mutation was the most frequently identified mutation. Screening for the most common mutations detected at least one mutation on 132/142 (93%) alleles. Multiple CYP21 mutations were detected on 16.2% of alleles. The high frequency of multiple mutations on a single allele emphasizes the importance of thorough and accurate molecular genotype analysis of the complex CYP21 locus.