Research Information System
53 rd Annual Meeting of the European Society for Paediatric Endocrinology (ESPE), Dublin, Ireland, 18 - 20 September 2014, vol.82, no.1, pp.176-177
Background: Nonclassical congenital adrenal hyperplasia
(NCAH), which is generally presented with symptoms of
androgen excess, is inherited autosomal recessive due to different
kind of mutations in the CYP21A2. Recently, high frequency of
copy number variations at CYP21A2 gene and predisposition of
heterozygous duplicated CYP21A2 for de novo gene aberrations
has been reported. Objective and hypotheses: To evaluate
clinical and moleculer characteristics of the patients with NCAH.
Method: Twenty-one patients (19F, 2M), diagnosed as NCAH
according to their clinical, hormonal, and molecular (biallelic or
monoallelic mutations) findings, were included. Sequencing and
multiplex ligation-dependent probe amplification (MLPA) were
used for moleculer analysis. Results: Mean age of the patients
at presentation was 10.5G4.1 (3.1–17.2) years. The presenting
symptoms were clinical hyperandrogenemia (hirsutism, acne, and
hair loss) (nZ10), premature adrenarche (nZ6), precocious
puberty (nZ5), menstrual irregularity (nZ2), and cliteromegaly
(nZ2). Mean of basal and peak 17-OH progesterone levels to
ACTH stimulation were 12.8G13.0 and 27.2G19.5 ng/ml
respectively. Cortisol responses to ACTH stimulation were
normal. Nine different mutations, including one novel were
detected in patients. Eight patients carried mutation in a single
allele. Two had heterozygous p.Q319X mutation with active gene
duplication. One patient carried two different (p.V282L and
p.P454S) mutations in a single allele. The p.454S was de novo in cis
position according to parental analysis and her father had active
gene duplication with p.Q319X mutation which wasn’t inherited.
Other patient with homozygous p.V282L also had novel de novo
heterozygous p.P214L mutation. Conclusion: As a result of
complex structure of CYP21A2 locus, not only sequencing but also
MLPA or southern blood methods should be performed to both
patients and parents. Much more comprehensive studies with
new genetic methods, including both offsprings and parents,
should be designed to exhibit clinical effects of variety of mutations
in NCAH.