A Novel POR G88S Mutation Causes Severe PORD and Establishes a Critical Pharmacogenomic Risk Profile

POR (p.Gly88Ser, homozygous — recurrent variant in 4 unrelated Argentine families)

Novel recurrent homozygous missense variant — translational clinical study + exhaustive in vitro functional characterization + pharmacogenomic profile (drug metabolism)

Report of 5 individuals from 4 unrelated Argentine families carrying the same homozygous POR p.Gly88Ser variant. The clinical picture is severe PORD with congenital adrenal hyperplasia. The study combines a paediatric clinical series with exhaustive in vitro molecular and functional characterization. Key original finding: the impact on CYP-dependent drug metabolism is precisely characterized, establishing a specific high-risk pharmacogenomic profile for this variant.

Synthesis written by Geno'X. For the full original abstract, please refer to the source publication.

Two points of direct clinical relevance: (1) recurrent variant to monitor in Argentine/Hispanic populations — to be recorded in ancestry-specific variant databases; (2) the established pharmacogenomic profile is directly actionable for drug prescriptions in PORD patients. Worth flagging in endocrine MDTs and genetics reviews.

known gene +0; biallelic AR +2; functional +2; 5 individuals 4 recurrent families +1; novel pharmacogenomic impact +1; J Clin Endocrinol Metab +1