Clinical Characteristics and Molecular Aetiology of Cytochrome P450 Oxidoreductase Deficiency Diagnosed in 46,XX Patients.

P450 oxidoreductase deficiency (PORD) affects cytochrome enzyme activities, causing various symptoms, such as adrenal insufficiency, disorders of sex development and skeletal malformations. This study aims to elucidate the clinical manifestations, genotype characteristics, diagnosis and management of 46,XX karyotype patients with PORD in China. A retrospective study included twelve 46,XX PORD patients in a Chinese tertiary medical center from 2004 to 2024. The patients' clinical characteristics were summarized based on manifestations, hormone profiles, and responses to treatments. The age of first visit was 7-31 years. Except for one young girl presenting with ambiguous genitalia since born, 11 patients presented with either abnormal menses or multiple ovarian cysts. Six patients showed masculinization of their external genitalia, and ten patients showed varying degrees of skeletal deformity. Progesterone was elevated and ovarian reserve was poor in all patients. The most frequent POR variant, c.1370G > A, located in exon 11 occurred in 11/12 patients with an allele frequency of 87.5% (21/24). Two novel nonsense mutations, c.1684dupG and c.2040dupC, were identified and assessed as pathogenic and likely pathogenic by ACMG, respectively. The c.1370G > A might be a dominant mutation type of POR in China. Female patients with PORD have a vulnerable ovarian reserve, and their ovarian macrocysts can be managed conservatively for fertility preservation. This study specifically focuses on PORD in 46,XX Chinese individuals, which implies its genetic causes with novel genetic findings and summarizes the puzzling spectrum of clinical manifestations.