biostudies-literatureKundishora AJNCATS NIH HHSNIA NIH HHSNHLBI NIH HHS993-1003https://www.ebi.ac.uk/biostudies/studies/S-EPMC8204259biostudies-literatureUnknown78(8)<h4>Importance</h4>Moyamoya disease (MMD), a progressive vasculopathy leading to narrowing and ultimate occlusion of the intracranial internal carotid arteries, is a cause of childhood stroke. The cause of MMD is poorly understood, but genetic factors play a role. Several familial forms of MMD have been identified, but the cause of most cases remains elusive, especially among non-East Asian individuals.<h4>Objective</h4>To assess whether ultrarare de novo and rare, damaging transmitted variants with large effect sizes are associated with MMD risk.<h4>Design, setting, and participants</h4>A genetic association study was conducted using whole-exome sequencing case-parent MMD trios in a small discovery cohort collected over 3.5 years (2016-2019); data were analyzed in 2020. Medical records frJAMA neurologyDIAPH1 Variants in Non-East Asian Patients With Sporadic Moyamoya Disease.PMC8204259UL1 TR001863T35 AG049685R00 HL143036R00 HL125683Dong WSmith ERBarak TOcken JDiab NSDuy PQWalker RLRoszko IGunel MKundishora AJPinard AZhao SNelson-Williams CMilewicz DMReeves BCLi BSujijantarat NRobert SMZhang BMatouk CCGeschwind DHZhao HStorm PBJin SCStratman ANDunbar ASmith HAlper SLNickerson DADuran DChen SLPanchagnula SMane SBamshad MJKahle KTCastaldi CKnight JRDiluna MLThumkeo DMiyagishima DFOrbach DBMarlier APeters STHaider SChen YHLopez-Giraldez FLifton RPLu QfalseDIAPH1 Variants in Non-East Asian Patients With Sporadic Moyamoya Disease.<h4>Importance</h4>Moyamoya disease (MMD), a progressive vasculopathy leading to narrowing and ultimate occlusion of the intracranial internal carotid arteries, is a cause of childhood stroke. The cause of MMD is poorly understood, but genetic factors play a role. Several familial forms of MMD have been identified, but the cause of most cases remains elusive, especially among non-East Asian individuals.<h4>Objective</h4>To assess whether ultrarare de novo and rare, damaging transmitted variants with large effect sizes are associated with MMD risk.<h4>Design, setting, and participants</h4>A genetic association study was conducted using whole-exome sequencing case-parent MMD trios in a small discovery cohort collected over 3.5 years (2016-2019); data were analyzed in 2020. Medical records fr2021-01-01T00:00:00Z2021 Aug2026-05-09T03:20:49.852Z2025-04-04T22:14:58.303ZS-EPMC82042593412515110.1001/jamaneurol.2021.1681