Rapid whole-genome sequencing identifies a novel AIRE variant associated with autoimmune polyendocrine syndrome type 1.

Autoimmune polyendocrine syndrome type 1 (APS-1; OMIM #240300), also referred to as autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED), is a rare monogenic autoimmune disorder caused by mutations in the autoimmune regulator (AIRE) gene. APS-1 is classically characterized by a triad of chronic mucocutaneous candidiasis, autoimmune hypoparathyroidism, and autoimmune adrenocortical insufficiency. We report a 5-yr-old female who presented with symptoms of tetany due to hypocalcemia and was subsequently found to be secondary to hypoparathyroidism. Rapid trio whole-genome sequencing revealed compound heterozygous variants in AIRE in the proband, with a paternally inherited, pathogenic, frameshift variant (c.1265delC; p.Pro422LeufsTer58) and a novel, likely pathogenic, maternally inherited missense variant (c.268T>C; p.Tyr90His).