ESPE Abstracts

Background: Steroid 17-hydroxylase deficiency (17OHD) (OMIM 202110) is a rare form of congenital adrenal hyperplasia caused by loss-of-function mutations in the 17α-hydroxylase (CYP17A1) gene. CYP17A1 is a key enzyme in the biosynthesis of adrenal and gonadal steroid hormones facilitating both 17α-hydroxylase and 17,20-lyase activities. The CYP17A1 gene is located on chromosome 10 and has eight coding exons. Herein, the molecular basis of 17OHD in a Kurdish family has been defined.

Objective and hypotheses: To characterize a partial CYP17A1 deletion in a family with 17α-hydroxylase deficiency by multiplex ligation-dependent probe amplification (MLPA).

Method: The index patient presented with amenorrhea and absence of secondary sexual characteristics. Further investigations established the diagnosis of 46,XY disorder of sex development (DSD). She is the daughter of consanguineous parents and has two sisters with similar clinical signs and symptoms.

Results: All patients had elevated concentrations of ACTH, gonadotropins, progesterone, in combination with decreased concentrations of cortisol, renin, testosterone and oestradiol. The molecular genetic analysis by PCR suggested a deletion spanning exons 1–6 of the CYP17A1 gene. MLPA analysis confirmed partial CYP17A1 deletion in patients and parents in homozygous and heterozygous state, respectively.

Conclusion: This is the first report employing MLPA as mutation analysis for the analysis of partial deletion of CYP17A1 gene affecting multiple exons in three patients with classic 17-hydroxylase deficiency. It appears important to consider large partial CYP17A1 deletions in 17OHD in addition to point mutation analysis in cases where no segregation analysis is possible to determine the correct genotype.