Phenotype/Genotype correlations in 21-hydroxylase deficiency

S. F. Siegel, P. A. Lee, W. A. Rudert, M. Swinyard, M. Trucco

Research output: Contribution to journalArticlepeer-review

21 Scopus citations


Study Objective: To correlate phenotype with genotype based on molecular diagnosis in patients with congenital adrenal hyperplasia due to 21-hydroxylase deficiency. Design: Polymerase chain reaction amplification, restriction fragment length polymorphism, and allele specific oligonucleotide hybridization were utilized to ascertain eight previously recognized deleterious mutations in affected individuals and their family members. Participants/Setting: DNA samples were obtained from 20 individuals with 21-hydroxylase deficiency followed through the Endocrine Clinic of the Children's Hospital of Pittsburgh. Fifteen individuals had salt-losing 21-hydroxylase deficiency and two families had two affected individuals. Four individuals presented prior to 5 years of age without salt loss. One individual presented in adolescence with hirsutism and oligomenorrhea. Main Outcome Measure: Molecular diagnosis of 21-hydroxylase deficiency. Results: Five patients have homozygous deletions of the promoter region. Two patients are homozygous for the splicing mutation in the second intron. Individual patients were homozygous for the following three mutations: Arg356 → TrP, Ile172 → Asn, and Val281 → Leu. Ten patients were compound heterozygotes. Conclusions: In general, the magnitude of enzyme activity correlates with the phenotypic findings. For example, mutations that completely impair enzyme activity, such as homozygous deletions of the promoter region, are associated with salt-losing congenital adrenal hyperplasia. However, the splicing mutation at nucleotide 655 in the second intron is characterized by greater phenotypic heterogeneity than the other mutations in this series.

Original languageEnglish (US)
Pages (from-to)9-16
Number of pages8
JournalAdolescent and Pediatric Gynecology
Issue number1
StatePublished - 1995

All Science Journal Classification (ASJC) codes

  • Pediatrics, Perinatology, and Child Health
  • Obstetrics and Gynecology


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