Introduction: Congenital adrenal hyperplasia (CAH) is an autosomal
recessively transmitted disease and 95% of CAH cases are
due to 21-hydroxylase deficiency (21-OHD). There are more than
100 mutations that cause CAH due to 21-OHD and the clinical expression
of the disease is reported to correlate with mutated alleles.
The aim: The aim of this study was to investigate responsible
mutations and then to evaluate genotype-phenotype relationship
in CAH patients with 21-OHD.
Methods: Mutations were firstly investigated by sequence
analysis by Sanger method; when needed Multiplex Ligation-dependent
Probe Amplification (MLPA) technique was applied. Mutations
were grouped as of group 0, A, B or C and compared with
the expected clinical phenotype i.e. Group 0: Salt wasting (SW),
Group A: SW, Group B: Simple virilizing (SV), Group C: Nonclassical
(NC) and positive predictive value (ppv) was determined for
the different groups (1).
Subjects: Genotype was investigated in 40 cases with 21-OHD
(33 classical, 7 nonclassical).
Results: Responsible mutations were determined in 37
of the cases (n:15 SW, n:15 SV, n:7 NC). The rate of parental
consanguinity was 43.2%. In 4 compound heterozygotes genotypes
were determined after the genotyping of parents. In 11 cases only
Sanger method, in 26 cases Sanger and MLPA methods were used.
Mutations were identified in 73 alleles from 37 cases (mutation
only in one allele in one case: Deletion/Not detected). The most
common mutation was IVS2-13A/C>G (28.3%), followed by
p.I172N mutation (17.5%) and large gene deletions (14.7%). In
addition, heterozygosity for p.Y59N mutation which has not been
previously reported in our region and a higher rate (10.8%) for the
p.V281L mutation than that reported before was found.