Although the proportion of MS patients harboring the RNF213 p.Asn2327Asp substitution is over the 75% threshold selected for positive co-segregation with disease, two patients without a family history of MS were found to have three or four unaffected siblings carrying the variant; thus not fulfilling our criteria for pathogenicity (Fig 2). The gene discussed is RNF213; the disease is myeloid sarcoma.