Clinical and genetic analysis for two Chinese siblings with 17α-hydroxylase/17,20-lyase deficiency

17α-hydroxylase/17,20-lyase deficiency (17OHD) is characterized by impaired productions of gonadal steroids and cortisol, a subsequent elevation of adrenocorticotropic hormone, and accumulation of steroid precusors, which are shunted into the mineralocorticoid synthesis pathway. This disease is caused by mutations in the CYP17 gene. In this paper, we will describe the clinical features and genetic alterations on two female siblings of 46,XY and 46,XX from a family with complete 17OHD.

This study employed a spectrum of methods, including clinical, hormonal, radiological and genetic analyses. Blood samples from the siblings and their family members were taken for genetic tests. Genomic DNA was extracted from peripheral blood leukocytes, and coding sequence abnormalities of the CYP17 gene were assessed by polymerase chain reaction and direct sequencing analysis.

Genetic analysis of the CYP17 gene revealed a homozygous mutation in the two siblings. The mutation is a microdeletion, located in exon 8, Asp487-Ser488-Phe489 deletion. This deletion may be a prevalent CYP17 mutation in the Chinese population.

Our study showed that a possible founder effect may account for the recurrent mutation Asp487-Ser488-Phe489 deletion in Chinese patients with 17OHD. And genetic testing could provide a useful method for a definitive diagnosis of 17OHD.