Genotype-phenotype analysis in congenital adrenal hyperplasia due to P450 oxidoreductase deficiency

摘要: Context: P450 oxidoreductase deficiency (PORD) is a unique congenital adrenal hyperplasia variant that manifests with glucocorticoid deficiency, disordered sex development (DSD), and skeletal malformations. No comprehensive data on genotype-phenotype correlations in Caucasian patients are available. Objective: The objective of the study was to establish large PORD cohort. Design: design clinical, biochemical, genetic assessment including multiplex ligation-dependent probe amplification (MLPA) 30 from 11 countries. Results: We identified 23 (POR) mutations (14 novel) an exonic deletion partial duplication detected by MLPA. Only 22% unrelated carried homozygous POR mutations. p.A287P most common mutation (43% alleles); no other hot spot identified. Urinary steroid profiling showed characteristic metabolomes variable impairment 17α-hydroxylase 21-hydroxylase. Short cosyntropin testing revealed insufficiency 89%. DSD present 15 18 46,XX seven 12 46,XY individuals. Homozygosity for invariably associated but normal genitalia majority mild moderate malformations, assessed novel scoring system, were compound heterozygous missense mutations, whereas nearly all severe malformations major loss-of-function defect one affected alleles. Conclusions: report findings cohort show MLPA useful addition analysis. frequent Caucasians, p.A287P, allows prediction genital phenotype Adrenal frequent, easily overlooked, readily testing.