Neurogenetics and Multi-omics of Neuroinflammatory Diseases in Multiplex Families to Improve Patients Health

The goal of this observational study is to learn why some families have several members with multiple sclerosis (MS), neuromyelitis optica spectrum disorder (NMOSD), or MOG antibody-associated disease (MOGAD). These diseases happen when the immune system attacks the brain, optic nerves, or spinal cord. The study includes about 500 people from about 100 families: people with one of these diseases and their relatives who do not have it. The main question is: Do rare gene changes (variants) shared by family members explain why these diseases run in families? Researchers will compare the DNA of family members who have the disease with the DNA of relatives who do not. They will also look at how genes are switched on and off in blood cells. Participants will: * Attend one visit of 2 to 3 hours at one of five French hospitals * Answer questions about their health, treatments, and family history * Give a 50 mL blood sample

Inclusion Criteria: * Affected participants: * Age 15 years and 3 months or older * Multiple sclerosis (2024 McDonald criteria), neuromyelitis optica spectrum disorder with anti-AQP4 antibodies (2015 Wingerchuk criteria), or MOG antibody-associated disease (2023 international MOGAD panel criteria) * Member of a multiplex family: at least two affected members sharing at least 12.5% of their genetic heritage * Affiliated to a social security scheme or equivalent * Written informed consent (for minors: assent of the minor and consent of the holders of parental authority) * Unaffected relatives: * Age 18 years or older * Sharing at least 25% of genetic heritage with one of the two affected family members * No multiple sclerosis, NMOSD, MOGAD, or other known inflammatory disease of the central nervous system * Affiliated to a social security scheme or equivalent * Written informed consent * Transcriptomic sub-cohort (30 to 60 participants, about 10 families): * Patients with no immunomodulatory or immunosuppressive treatment for at least 12 months, and their relatives Exclusion Criteria: * Refusal to participate before the inclusion visit * Inability to understand the study information or to consent * Person under guardianship, curatorship or legal protection * Person deprived of liberty by judicial or administrative decision * Pregnant or breastfeeding woman * No kinship with at least one affected member of the included family * Refusal to be informed of an incidental discovery of a pathogenic genetic variant