Association of De Novo RNF213 Variants With Childhood Onset Moyamoya Disease and Diffuse Occlusive Vasculopathy.

Autor:	Pinard A; From the Department of Internal Medicine (A.P., A.C.C., M.A., D.G., D.M.M.), McGovern Medical School, University of Texas Health Science Center at Houston; Maritime Medical Genetics Service (A.L.R., S.P., M.A.V.), Division of Neurosurgery (M.D.J.F., P.D.M., S.W.) and Department of Pediatrics (M.A.V.), Division of Medical Genetics, Dalhousie University, IWK Health Centre Halifax, Nova Scotia Canada; Department of Pediatrics (S.C.N.), Division of Child Neurology, and Department of Genetics (A.C.E.H.), University of Alabama at Birmingham; Department of Pediatrics (M.J.B., A.M.V.), Division of Genetics Medicine and Department of Genome Sciences (M.J.B., D.A.N.), University of Washington, Seattle; and Department of Pediatrics (S.M.F.), Division of Child Neurology, University of Texas McGovern Medical School., Fiander MDJ; From the Department of Internal Medicine (A.P., A.C.C., M.A., D.G., D.M.M.), McGovern Medical School, University of Texas Health Science Center at Houston; Maritime Medical Genetics Service (A.L.R., S.P., M.A.V.), Division of Neurosurgery (M.D.J.F., P.D.M., S.W.) and Department of Pediatrics (M.A.V.), Division of Medical Genetics, Dalhousie University, IWK Health Centre Halifax, Nova Scotia Canada; Department of Pediatrics (S.C.N.), Division of Child Neurology, and Department of Genetics (A.C.E.H.), University of Alabama at Birmingham; Department of Pediatrics (M.J.B., A.M.V.), Division of Genetics Medicine and Department of Genome Sciences (M.J.B., D.A.N.), University of Washington, Seattle; and Department of Pediatrics (S.M.F.), Division of Child Neurology, University of Texas McGovern Medical School., Cecchi AC; From the Department of Internal Medicine (A.P., A.C.C., M.A., D.G., D.M.M.), McGovern Medical School, University of Texas Health Science Center at Houston; Maritime Medical Genetics Service (A.L.R., S.P., M.A.V.), Division of Neurosurgery (M.D.J.F., P.D.M., S.W.) and Department of Pediatrics (M.A.V.), Division of Medical Genetics, Dalhousie University, IWK Health Centre Halifax, Nova Scotia Canada; Department of Pediatrics (S.C.N.), Division of Child Neurology, and Department of Genetics (A.C.E.H.), University of Alabama at Birmingham; Department of Pediatrics (M.J.B., A.M.V.), Division of Genetics Medicine and Department of Genome Sciences (M.J.B., D.A.N.), University of Washington, Seattle; and Department of Pediatrics (S.M.F.), Division of Child Neurology, University of Texas McGovern Medical School., Rideout AL; From the Department of Internal Medicine (A.P., A.C.C., M.A., D.G., D.M.M.), McGovern Medical School, University of Texas Health Science Center at Houston; Maritime Medical Genetics Service (A.L.R., S.P., M.A.V.), Division of Neurosurgery (M.D.J.F., P.D.M., S.W.) and Department of Pediatrics (M.A.V.), Division of Medical Genetics, Dalhousie University, IWK Health Centre Halifax, Nova Scotia Canada; Department of Pediatrics (S.C.N.), Division of Child Neurology, and Department of Genetics (A.C.E.H.), University of Alabama at Birmingham; Department of Pediatrics (M.J.B., A.M.V.), Division of Genetics Medicine and Department of Genome Sciences (M.J.B., D.A.N.), University of Washington, Seattle; and Department of Pediatrics (S.M.F.), Division of Child Neurology, University of Texas McGovern Medical School., Azouz M; From the Department of Internal Medicine (A.P., A.C.C., M.A., D.G., D.M.M.), McGovern Medical School, University of Texas Health Science Center at Houston; Maritime Medical Genetics Service (A.L.R., S.P., M.A.V.), Division of Neurosurgery (M.D.J.F., P.D.M., S.W.) and Department of Pediatrics (M.A.V.), Division of Medical Genetics, Dalhousie University, IWK Health Centre Halifax, Nova Scotia Canada; Department of Pediatrics (S.C.N.), Division of Child Neurology, and Department of Genetics (A.C.E.H.), University of Alabama at Birmingham; Department of Pediatrics (M.J.B., A.M.V.), Division of Genetics Medicine and Department of Genome Sciences (M.J.B., D.A.N.), University of Washington, Seattle; and Department of Pediatrics (S.M.F.), Division of Child Neurology, University of Texas McGovern Medical School., Fraser SM; From the Department of Internal Medicine (A.P., A.C.C., M.A., D.G., D.M.M.), McGovern Medical School, University of Texas Health Science Center at Houston; Maritime Medical Genetics Service (A.L.R., S.P., M.A.V.), Division of Neurosurgery (M.D.J.F., P.D.M., S.W.) and Department of Pediatrics (M.A.V.), Division of Medical Genetics, Dalhousie University, IWK Health Centre Halifax, Nova Scotia Canada; Department of Pediatrics (S.C.N.), Division of Child Neurology, and Department of Genetics (A.C.E.H.), University of Alabama at Birmingham; Department of Pediatrics (M.J.B., A.M.V.), Division of Genetics Medicine and Department of Genome Sciences (M.J.B., D.A.N.), University of Washington, Seattle; and Department of Pediatrics (S.M.F.), Division of Child Neurology, University of Texas McGovern Medical School., McNeely PD; From the Department of Internal Medicine (A.P., A.C.C., M.A., D.G., D.M.M.), McGovern Medical School, University of Texas Health Science Center at Houston; Maritime Medical Genetics Service (A.L.R., S.P., M.A.V.), Division of Neurosurgery (M.D.J.F., P.D.M., S.W.) and Department of Pediatrics (M.A.V.), Division of Medical Genetics, Dalhousie University, IWK Health Centre Halifax, Nova Scotia Canada; Department of Pediatrics (S.C.N.), Division of Child Neurology, and Department of Genetics (A.C.E.H.), University of Alabama at Birmingham; Department of Pediatrics (M.J.B., A.M.V.), Division of Genetics Medicine and Department of Genome Sciences (M.J.B., D.A.N.), University of Washington, Seattle; and Department of Pediatrics (S.M.F.), Division of Child Neurology, University of Texas McGovern Medical School., Walling S; From the Department of Internal Medicine (A.P., A.C.C., M.A., D.G., D.M.M.), McGovern Medical School, University of Texas Health Science Center at Houston; Maritime Medical Genetics Service (A.L.R., S.P., M.A.V.), Division of Neurosurgery (M.D.J.F., P.D.M., S.W.) and Department of Pediatrics (M.A.V.), Division of Medical Genetics, Dalhousie University, IWK Health Centre Halifax, Nova Scotia Canada; Department of Pediatrics (S.C.N.), Division of Child Neurology, and Department of Genetics (A.C.E.H.), University of Alabama at Birmingham; Department of Pediatrics (M.J.B., A.M.V.), Division of Genetics Medicine and Department of Genome Sciences (M.J.B., D.A.N.), University of Washington, Seattle; and Department of Pediatrics (S.M.F.), Division of Child Neurology, University of Texas McGovern Medical School., Novara SC; From the Department of Internal Medicine (A.P., A.C.C., M.A., D.G., D.M.M.), McGovern Medical School, University of Texas Health Science Center at Houston; Maritime Medical Genetics Service (A.L.R., S.P., M.A.V.), Division of Neurosurgery (M.D.J.F., P.D.M., S.W.) and Department of Pediatrics (M.A.V.), Division of Medical Genetics, Dalhousie University, IWK Health Centre Halifax, Nova Scotia Canada; Department of Pediatrics (S.C.N.), Division of Child Neurology, and Department of Genetics (A.C.E.H.), University of Alabama at Birmingham; Department of Pediatrics (M.J.B., A.M.V.), Division of Genetics Medicine and Department of Genome Sciences (M.J.B., D.A.N.), University of Washington, Seattle; and Department of Pediatrics (S.M.F.), Division of Child Neurology, University of Texas McGovern Medical School., Hurst ACE; From the Department of Internal Medicine (A.P., A.C.C., M.A., D.G., D.M.M.), McGovern Medical School, University of Texas Health Science Center at Houston; Maritime Medical Genetics Service (A.L.R., S.P., M.A.V.), Division of Neurosurgery (M.D.J.F., P.D.M., S.W.) and Department of Pediatrics (M.A.V.), Division of Medical Genetics, Dalhousie University, IWK Health Centre Halifax, Nova Scotia Canada; Department of Pediatrics (S.C.N.), Division of Child Neurology, and Department of Genetics (A.C.E.H.), University of Alabama at Birmingham; Department of Pediatrics (M.J.B., A.M.V.), Division of Genetics Medicine and Department of Genome Sciences (M.J.B., D.A.N.), University of Washington, Seattle; and Department of Pediatrics (S.M.F.), Division of Child Neurology, University of Texas McGovern Medical School., Guo D; From the Department of Internal Medicine (A.P., A.C.C., M.A., D.G., D.M.M.), McGovern Medical School, University of Texas Health Science Center at Houston; Maritime Medical Genetics Service (A.L.R., S.P., M.A.V.), Division of Neurosurgery (M.D.J.F., P.D.M., S.W.) and Department of Pediatrics (M.A.V.), Division of Medical Genetics, Dalhousie University, IWK Health Centre Halifax, Nova Scotia Canada; Department of Pediatrics (S.C.N.), Division of Child Neurology, and Department of Genetics (A.C.E.H.), University of Alabama at Birmingham; Department of Pediatrics (M.J.B., A.M.V.), Division of Genetics Medicine and Department of Genome Sciences (M.J.B., D.A.N.), University of Washington, Seattle; and Department of Pediatrics (S.M.F.), Division of Child Neurology, University of Texas McGovern Medical School., Parkash S; From the Department of Internal Medicine (A.P., A.C.C., M.A., D.G., D.M.M.), McGovern Medical School, University of Texas Health Science Center at Houston; Maritime Medical Genetics Service (A.L.R., S.P., M.A.V.), Division of Neurosurgery (M.D.J.F., P.D.M., S.W.) and Department of Pediatrics (M.A.V.), Division of Medical Genetics, Dalhousie University, IWK Health Centre Halifax, Nova Scotia Canada; Department of Pediatrics (S.C.N.), Division of Child Neurology, and Department of Genetics (A.C.E.H.), University of Alabama at Birmingham; Department of Pediatrics (M.J.B., A.M.V.), Division of Genetics Medicine and Department of Genome Sciences (M.J.B., D.A.N.), University of Washington, Seattle; and Department of Pediatrics (S.M.F.), Division of Child Neurology, University of Texas McGovern Medical School., Bamshad MJ; From the Department of Internal Medicine (A.P., A.C.C., M.A., D.G., D.M.M.), McGovern Medical School, University of Texas Health Science Center at Houston; Maritime Medical Genetics Service (A.L.R., S.P., M.A.V.), Division of Neurosurgery (M.D.J.F., P.D.M., S.W.) and Department of Pediatrics (M.A.V.), Division of Medical Genetics, Dalhousie University, IWK Health Centre Halifax, Nova Scotia Canada; Department of Pediatrics (S.C.N.), Division of Child Neurology, and Department of Genetics (A.C.E.H.), University of Alabama at Birmingham; Department of Pediatrics (M.J.B., A.M.V.), Division of Genetics Medicine and Department of Genome Sciences (M.J.B., D.A.N.), University of Washington, Seattle; and Department of Pediatrics (S.M.F.), Division of Child Neurology, University of Texas McGovern Medical School., Nickerson DA; From the Department of Internal Medicine (A.P., A.C.C., M.A., D.G., D.M.M.), McGovern Medical School, University of Texas Health Science Center at Houston; Maritime Medical Genetics Service (A.L.R., S.P., M.A.V.), Division of Neurosurgery (M.D.J.F., P.D.M., S.W.) and Department of Pediatrics (M.A.V.), Division of Medical Genetics, Dalhousie University, IWK Health Centre Halifax, Nova Scotia Canada; Department of Pediatrics (S.C.N.), Division of Child Neurology, and Department of Genetics (A.C.E.H.), University of Alabama at Birmingham; Department of Pediatrics (M.J.B., A.M.V.), Division of Genetics Medicine and Department of Genome Sciences (M.J.B., D.A.N.), University of Washington, Seattle; and Department of Pediatrics (S.M.F.), Division of Child Neurology, University of Texas McGovern Medical School., Vandersteen AM; From the Department of Internal Medicine (A.P., A.C.C., M.A., D.G., D.M.M.), McGovern Medical School, University of Texas Health Science Center at Houston; Maritime Medical Genetics Service (A.L.R., S.P., M.A.V.), Division of Neurosurgery (M.D.J.F., P.D.M., S.W.) and Department of Pediatrics (M.A.V.), Division of Medical Genetics, Dalhousie University, IWK Health Centre Halifax, Nova Scotia Canada; Department of Pediatrics (S.C.N.), Division of Child Neurology, and Department of Genetics (A.C.E.H.), University of Alabama at Birmingham; Department of Pediatrics (M.J.B., A.M.V.), Division of Genetics Medicine and Department of Genome Sciences (M.J.B., D.A.N.), University of Washington, Seattle; and Department of Pediatrics (S.M.F.), Division of Child Neurology, University of Texas McGovern Medical School., Milewicz DM; From the Department of Internal Medicine (A.P., A.C.C., M.A., D.G., D.M.M.), McGovern Medical School, University of Texas Health Science Center at Houston; Maritime Medical Genetics Service (A.L.R., S.P., M.A.V.), Division of Neurosurgery (M.D.J.F., P.D.M., S.W.) and Department of Pediatrics (M.A.V.), Division of Medical Genetics, Dalhousie University, IWK Health Centre Halifax, Nova Scotia Canada; Department of Pediatrics (S.C.N.), Division of Child Neurology, and Department of Genetics (A.C.E.H.), University of Alabama at Birmingham; Department of Pediatrics (M.J.B., A.M.V.), Division of Genetics Medicine and Department of Genome Sciences (M.J.B., D.A.N.), University of Washington, Seattle; and Department of Pediatrics (S.M.F.), Division of Child Neurology, University of Texas McGovern Medical School. Dianna.M.Milewicz@uth.tmc.edu.
Jazyk:	angličtina
Zdroj:	Neurology [Neurology] 2021 Mar 30; Vol. 96 (13), pp. e1783-e1791. Date of Electronic Publication: 2021 Feb 10.
DOI:	10.1212/WNL.0000000000011653
Abstrakt:	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 RNF213 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 RNF213 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. (© 2021 American Academy of Neurology.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu