Who is a carrier? Detection of unsuspected mutations in 21-hydroxylase deficiency

Selma Siegel Witchel, Peter A. Lee, Massimo Trucco

Research output: Contribution to journalArticlepeer-review

17 Scopus citations


Congenital adrenal hyperplasia due to 21-hydroxylase deficiency is a common autosomal-recessive disorder. During our routine genotyping of affected individuals and their relatives using allele-specific oligonucleotide hybridization and single-strand conformational polymorphism analysis, we identified two families each segregating three mutations. In both families, a mutation known to be associated with 21-hydroxylase deficiency was identified in healthy individuals but was not detected in the propositus. The propositus in family 1 was shown to be a homozygous carrier for G at nucleotide 655, which alters the splice acceptor site at exon 3. The propositus in family 2 carried the same splicing mutation on the maternal allele and a gene deletion/conversion on the paternal allele. In both families, other clinically unaffected relatives carried the Q318X mutation in exon 8. If molecular diagnostic studies had been limited to the mutation carried by the propositi, relatives would have been misinformed regarding their status as carriers or mildly affected individuals. The findings in these two families emphasize the high frequency of alleles causing 21- hydroxylase deficiency in the population.

Original languageEnglish (US)
Pages (from-to)2-9
Number of pages8
JournalAmerican Journal of Medical Genetics
Issue number1
StatePublished - Jan 2 1996

All Science Journal Classification (ASJC) codes

  • Genetics
  • Genetics(clinical)


Dive into the research topics of 'Who is a carrier? Detection of unsuspected mutations in 21-hydroxylase deficiency'. Together they form a unique fingerprint.

Cite this