Identification of a novel large CYP17A1 deletion by MLPA analysis in a family with classic 17α-hydroxylase deficiency.

Steroid 17α-hydroxylase deficiency (17OHD) is a rare form of congenital adrenal hyperplasia caused by 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. We characterized a partial CYP17A1 deletion in a Kurdish family with 17OHD by multiplex ligation-dependent probe amplification (MLPA). The index patient presented with amenorrhea and lack of pubertal development. Investigations established the diagnosis of 46,XY disorder of sex development (DSD). She is the daughter of consanguineous parents and has 2 sisters with similar clinical presentation. All patients showed biochemical signs of primary adrenal and gonadal insufficiency. The molecular genetic analysis by PCR suggested a deletion spanning exons 1–6 of the CYP17A1 gene. MLPA analysis confirmed the large partial CYP17A1 deletion in patients and parents in homozygous and heterozygous state, respectively. This is the first report employing MLPA for mutation analysis to detect a deletion of CYP17A1 spanning multiple exons in 3 patients with classic 17OHD. Therefore, it is important to consider large partial CYP17A1 deletions in 17OHD in addition to point mutations in cases where no segregation analysis is possible to determine the correct genotype.