First Case of V281+I172N/V281L CYP21A2 Genotype Associated with Congenital Adrenal Hyperplasia: A Case Report from Southern Italy

The document reports the first case of a new genotype associated with non-classical congenital adrenal hyperplasia (NC-CAH), identified in two siblings from Southern Italy. The genotype, V281+I172N/V281L, was determined through direct genetic sequencing of the CYP21A2 gene. The 31-year-old female patient exhibited symptoms such as oligo-amenorrhea, hirsutism, mild acne, and mild hyperinsulinism, while the 28-year-old male patient presented with androgenic alopecia and oligo-therato-zoospermia. Both siblings were successfully treated with dexamethasone. Laboratory tests showed elevated basal 17-OH progesterone and ACTH levels, particularly in the male patient. The parents were carriers of the mutations, with the father bearing both V281L and I172N mutations and the mother only the V281L mutation. The study concludes that this new genotype should be included in the panel of mutations associated with NC-CAH and suggests that further research is needed to evaluate the prevalence of this genotype, especially in mild or subclinical forms of the disease.