Objective: To investigate the clinical and molecular characteristics of a girl with 17α hydroxylase/17,20-lyase deficiency, of which, onset was as rhabdomyolysis and hypokalemia. And then we identified the functional consequences of two novel CYP17A1 mutations.
Materials and Methods: A 11 years old girl, 46,XX karyotypes, presented with rhabdomyolysis, hypokalemia and hypertension. She had elevated levels of plasma adrenocorticotropic hormone, serum gonadotropin and progesterone, and reduced cortisol, testosterone, dehydroepiandrosterone sulfate (DHEA-S) and plasma renin activity (PRA). All coding exons sequences of CYP17A1 were directly sequenced using genomic DNA. Wild-type and mutant CYP17A1 cDNAs were inserted into the pcDNA3.1(+) vector, and transiently expressed in HEK-293T cells. This was followed by an assessment of 17α-hydroxylase and 17,20-lyase activities by measuring the conversions of progesterone to 17-hydroxyprogesterone and 17-hydroxypregnenolone to DHEA.
Results: The mutation analysis identified one patient with compound heterozygosity [c.1304T>C/p.F435S;c.1228delG/p.D410Ifs*9]. An in vitro functional analysis of both novel p.P435S and p.D410Ifs*9 mutations revealed a complete loss of 17α-hydroxylase/17, 20-lyase activities.
Conclusion: We present a case of combined deficiency of 17a-hydroxylase/17,20-lyase caused by compound heterozygosity for two novel mutations in the CYP17A1 gene. Rhabdomyolysis may be a complication of 17OHD or its initial performance. In such cases, it is mandatory to assess the perform hormonal and molecular genetic studies.
27 - 29 Sep 2018
European Society for Paediatric Endocrinology