Genotype and phenotype charasterictics of patients with nonclassical congenital adrenal hyperplasia due to 21-hydroxylase deficiency

Akcan Tombalak N., Toksoy G. , Uyguner Z. O. , Karakılıç Özturan E. , Aydın B., Baş F. , ...Daha Fazla

53 rd Annual Meeting of the European Society for Paediatric Endocrinology (ESPE), Dublin, İrlanda, 18 - 20 Eylül 2014, cilt.82, no.1, ss.176-177

  • Cilt numarası: 82
  • Basıldığı Şehir: Dublin
  • Basıldığı Ülke: İrlanda
  • Sayfa Sayıları: ss.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.