Background Current methods for the molecular diagnosis of the
21-hydroxylase deficiency variant of congenital adrenal hyperplasia use cumbersome
combinations of Southern blotting and polymerase chain reaction (PCR). The aim of the
present study was to develop a practical genetic test for the unambiguous diagnosis
of this condition, and to use this procedure to determine the range of mutations in
Scottish patients. In addition, we wished to obtain further information to that
currently available in the literature regarding the correlation of genotype with
phenotype in any identified carriers. Methods We studied five Scottish
probands and their family members. To try to obviate the need for Southern blotting,
we investigated a technique that uses the oligoligation chain reaction after
gene-specific PCR. Results We found a spectrum of mutations in the ten
unrelated mutant alleles studied. These consisted of at least three different 30-kb
deletions, two intron 2 splice-site mutations and single occurrences of the I172N,
V281L and R356W substitutions. Conclusions The genotype-phenotype
correlations agreed with those previously described. In addition, our results suggest
that there is no predominant Scottish genotype.
