A novel mutation found in a patient with congenital adrenal hyperplasia

Background: Congenital adrenal hyperplasia (CAH) is a group of autosomal recessive disorders demonstrated by a failure in one of the five enzymes responsible for cortisol production. The disorder represents itself by low blood levels of estrogens, androgens, and cortisol that generally pair with hypertension, Hypokalemia, sexual infantilism and primary amenorrhea in affected individuals.Objective: A 14-yr-old female, the first child of consanguineous parents with normal family history was referred to genetic clinic with high blood pressure, ambiguous genitalia, and lack of pubertal development. No pubic or axillary hair was seen by physical examination, and she had no clinical symptoms of Turner syndrome. She was hypertensive (150/90 mmHg, 50th percentile for age) with high gonadotropins levels (LH, 19 mU/mL; FSH, 34 mU/mL). Moreover, low peripheral concentrations of sex steroids were seen.Materials and Methods: Sonographic and karyotyping method was performed. Genomic DNA was isolated from peripheral blood. All eight exons of CYP17A1 gene were multiplied by PCR. Products were sequenced.Results: The karyotype was normal (46, XX) and in sonographic survey uterus was infantile. Sanger Sequence chromatogram of the CYP17A1 gene show A new in-frame homozygous deletion c.1052-1054CCT in exon 6 (deletion of 351Leu in protein and CCT deletion on cDNA sequence).Conclusion: Deficiency of CYP17A1, the hormonal alterations are summarized as sex steroids and cortisol insufficiencies with mineralocorticoids excess. This case manifested typical feature of 17α-hydroxylase and 17,20-lyase deficiencies. This study report an in-frame deletion which leads to isolated 17,20-lyase deficiency and this mutation may be used for diagnosis in other patients with typical clinical symptoms. Diagnosis of 17α hydroxylase/17,20 lyase deficiency was confirmed by the specific profile of adrenal steroid levels, and further confirmation by CYP17A mutation analysis.

Keywords:

Congenital adrenal hyperplasia (CAH) , CYP17A1 gene , Ambiguous genitalia