|Title||Association of De Novo Variants With Childhood Onset Moyamoya Disease and Diffuse Occlusive Vasculopathy.|
|Publication Type||Journal Article|
|Year of Publication||2021|
|Authors||Pinard, A, Fiander, MDJ, Cecchi, AC, Rideout, AL, Azouz, M, Fraser, SM, P McNeely, D, Walling, S, Novara, SC, Hurst, ACE, Guo, D, Parkash, S, Bamshad, MJ, Nickerson, DA, Vandersteen, AM, Milewicz, DM|
|Date Published||2021 03 30|
|Keywords||Adenosine Triphosphatases, Adult, Age of Onset, Aortic Diseases, Arterial Occlusive Diseases, Child, Preschool, Female, Femoral Artery, Humans, Iliac Artery, Male, Moyamoya Disease, Mutation, Renal Artery Obstruction, Ubiquitin-Protein Ligases|
OBJECTIVE: To test the hypothesis that de novo genetic variants are responsible for moyamoya disease (MMD) in children with unaffected relatives, we performed exome sequencing of 28 affected children and their unaffected parents.
METHODS: Exome sequencing was performed on 28 trios of affected patients with MMD and unaffected parents.
RESULTS: We identified 3 novel rare de novo variants, 1 in the RING domain and 2 in a highly conserved region distal to the RING domain (4,114-4,120). These de novo cases of MMD present at a young age with aggressive MMD and uniquely have additional occlusive vascular lesions, including renal artery stenosis. Two previously reported cases had de novo variants in the same limited region and presented young with aggressive MMD, and 1 case had narrowing of the inferior abdominal aorta.
CONCLUSIONS: These results indicate a novel syndrome associated with rare variants defined by de novo mutations disrupting highly conserved amino acids in the RING domain and a discrete region distal to the RING domain delimited by amino acids 4,114 to 4,120 leading to onset of severe MMD before 3 years of age and occlusion of other arteries, including the abdominal aorta, renal, iliac, and femoral arteries.
|PubMed Central ID||PMC8055312|
|Grant List||UM1 HG006493 / HG / NHGRI NIH HHS / United States |
R01 HL109942 / HL / NHLBI NIH HHS / United States