1. Genotype-Phenotype Correlation in Long-Term Cohort of Japanese Patients with Moyamoya Disease.
- Author
-
Nomura S, Yamaguchi K, Akagawa H, Kawashima A, Moteki Y, Ishikawa T, Aihara Y, Saito T, Okada Y, and Kawamata T
- Subjects
- Adolescent, Adult, Brain Infarction diagnosis, Brain Infarction surgery, Cerebral Hemorrhage diagnosis, Cerebral Hemorrhage surgery, Cerebral Intraventricular Hemorrhage diagnosis, Cerebral Intraventricular Hemorrhage genetics, Cerebral Intraventricular Hemorrhage surgery, Cerebral Revascularization, Child, Child, Preschool, Genetic Association Studies, Genetic Predisposition to Disease, Humans, Infant, Ischemic Attack, Transient diagnosis, Ischemic Attack, Transient surgery, Middle Aged, Moyamoya Disease diagnosis, Moyamoya Disease therapy, Phenotype, Progression-Free Survival, Recurrence, Retrospective Studies, Risk Factors, Time Factors, Tokyo, Young Adult, Adenosine Triphosphatases genetics, Brain Infarction genetics, Cerebral Hemorrhage genetics, Genetic Variation, Ischemic Attack, Transient genetics, Moyamoya Disease genetics, Ubiquitin-Protein Ligases genetics
- Abstract
Background: Homozygosity of this p.R4810K founder variant of RNF213moyamoya disease (MMD) susceptibility gene is known to influence the severity of the clinical disease phenotype at disease onset. However, the association between this genotype and long-term clinical manifestations has remained unclear., Objectives: The principal goal of this study was to investigate whether and how the p.R4810K variant of RNF213influences the long-term phenotype in Japanese patients with MMD., Method: This retrospective cohort study included 94 Japanese patients with MMD who underwent direct or combined bypass for revascularization with the p.R4810K genotype determined in our hospital. The following phenotypic parameters were analyzed at disease onset and over a long-term period: age and initial presentation at onset, recurrent stroke after initial revascularization, and final modified Rankin Scale., Results: The p.R4810K genotype was significantly associated with the phenotype at onset, especially in younger patients. Over a median follow-up period of 100 months, recurrent stroke occurred in 6 out of 94 patients: none out of 5 patients with the homozygous variant, 5 out of 64 with the heterozygous variant, and 1 out of 25 in the wild-type group. There were no significant differences among the genotypes. In particular, recurrent cerebral hemorrhage occurred in 5 patients, all possessing the heterozygous variant. The log-rank test showed no difference between the genotypes in the stroke-free survival rate. Furthermore, the p.R4810K genotype was not associated with a poor functional condition., Conclusions: The p.R4810K founder variant of RNF213 affects the phenotype at disease onset. However, the optimal revascularization may be effective, regardless of the genotype, even for the homozygous variant, which has been thought to be the most pathogenic. This genotype may not strongly influence the long-term clinical manifestations or poor prognosis in MMD., (© 2019 S. Karger AG, Basel.)
- Published
- 2019
- Full Text
- View/download PDF