Absence of Pathogenic Mutations and Strong Association With HLA-DRB1*11:01 in Statin-Naïve Early-Onset Anti-HMGCR Necrotizing Myopathy.
Laura LlansóAlba Segarra-CasasCristina Domínguez-GonzálezEdoardo MalfattiSolange KapetanovicBenjamín Rodríguez-SantiagoOscar de la CalleRosa BlancoAmelia DobrescuAndrés Nascimento-OsorioAndrés PaipaAurelio Hernandez-LainCristina JouAnaís MariscalLaura González-MeraAna ArtecheCinta LleixàMarta Caballero-ÁvilaÁlvaro CarbayoAna VesperinasLuis Antonio Querol-GutiérrezEduard GallardoMontse OlivéPublished in: Neurology(R) neuroimmunology & neuroinflammation (2024)
WES of a cohort of patients with dystrophy-like anti-HMGCR IMNM did not reveal any common rare variants of any gene, including cholesterol biosynthesis-related genes. HLA analysis showed a strong association with HLA-DRB1*11:01, previously mostly described in statin-exposed adult patients; consequently, a common immunogenic predisposition should be suspected, irrespective of statin exposure. Moreover, we were unable to conclusively demonstrate muscle upregulation/mislocalization of HMGCR in IMNM, whether or not driven by statins.