William Dobyns, MD

Dr. Dobyns is Professor of Pediatrics and Director of the Division of Genetics and Metabolism at the University of Minnesota. He joined the Faculty in June 2020 for his second tour at the U, having worked in the Division of Pediatric Neurology from 1992-1998. He is a physician-scientist who studies the nature and causes of developmental brain disorders, and is a leading authority on the causes of human brain malformations. While best known for his work on lissencephaly (smooth brain) and megalencephaly (enlarged brain), he provided the original descriptions for more than 10 clinically recognizable and now well-known syndromes including Smith-Magenis syndrome, rapid-onset dystonia-parkinsonism, coloboma-renal syndrome, bilateral frontoparietal cobblestone malformation, megalencephaly-capillary malformation syndrome (MCAP), megalencephaly-polymicrogyria-polydactly-hydrocephalus syndrome (MPPH) and X-linked lissencephaly with abnormal genitalia (XLAG), all of these now linked to the underlying gene or genes. He co-discovered at least 14 pathogenic copy number variants including the well-known deletion 17p13.3 (Miller-Dieker syndrome), deletion 17p11.2 (Smith-Magenis syndrome) and deletion 16p11.2 (autism and intellectual disability), and co-discovered almost 70 human disease genes. 

Dr. Dobyns has also designed and published the major classification systems now in use for brain malformation, and several of the terms that we now use for these disorders come from his work, for example: "malformations of cortical development"; "cobblestone malformation", and "dysgyria". He has also made contributions on the causes of neurodegenerative disorders and developmental disorders of other systems, such as vascular malformations. Dr. Dobyns has served as Principle Investigator on major NIH grants since 1999, and recently published his 400th peer-reviewed scientific paper. In recognition of these and other accomplishments, he received the 2018 Bernard Sachs Award for research in neuroscience with relevance to the care of children with neurological disorders from the Child Neurology Society. 

• Bernard Sachs Award for research in neuroscience with relevance to the care of children with neurological disorders, Child Neurology Society (2018)

Neurodevelopmental disorders especially those associated with abnormal brain size, malformations and epilepsy, vascular malformations, mosaicism. 

Aldinger KA, Timms AE, Thomson Z, Mirzaa GM, Bennett JT, Rosenberg AB, Roco CM, Hirano M, Abidi F, Haldipur P, Cheng CV, Collins S, Park K, Zeiger J, Overmann LM, Alkuraya FS, Biesecker LG, Braddock SR, Cathey S, Cho MT, Chung BHY, Everman DB, Zarate YA, Jones JR, Schwartz CE, Goldstein A, Hopkin RJ, Krantz ID, Ladda RL, Leppig KA, McGillivray BC, Sell S, Wusik K, Gleeson JG, Nickerson DA, Bamshad MJ, Gerrelli D, Lisgo SN, Seelig G, Ishak GE, Barkovich AJ, Curry CJ, Glass IA, Millen KJ, Doherty D, Dobyns WB. Redefining the Etiologic Landscape of Cerebellar Malformations. Am J Hum Genet 2019; 105: 606-615. PMID 31474318 PMC6731369

Dobyns WB, Aldinger KA, Ishak GE, Mirzaa GM, Timms AE, Grout ME, Dremmen MHG, Schot R, Vandervore L, van Slegtenhorst MA, Wilke M, Kasteleijn E, Lee AS, Barry BJ, Chao KR, Szczaluba K, Kobori J, Hanson-Kahn A, Bernstein JA, Carr L, D'Arco F, Miyana K, Okazaki T, Saito Y, Sasaki M, Das S, Wheeler MM, Bamshad MJ, Nickerson DA, University of Washington Center for Mendelian G, Center for Mendelian Genomics at the Broad Institute of MIT, Harvard, Engle EC, Verheijen FW, Doherty D, Mancini GMS. MACF1 Mutations Encoding Highly Conserved Zinc-Binding Residues of the GAR Domain Cause Defects in Neuronal Migration and Axon Guidance. Am J Hum Genet 2018; 103: 1009-1021. PMID 30471716 PMC6288423

Dobyns WB, Stratton RF, Parke JT, Greenberg F, Nussbaum RL, Ledbetter DH. Miller-Dieker syndrome: lissencephaly and monosomy 17p. J Pediatr 1983; 102: 552-8. PMID 6834189

Riviere JB, Mirzaa GM, O'Roak BJ, Beddaoui M, Alcantara D, Conway RL, St-Onge J, Schwartzentruber JA, Gripp KW, Nikkel SM, Worthylake T, Sullivan CT, Ward TR, Butler HE, Kramer NA, Albrecht B, Armour CM, Armstrong L, Caluseriu O, Cytrynbaum C, Drolet BA, Innes AM, Lauzon JL, Lin AE, Mancini GM, Meschino WS, Reggin JD, Saggar AK, Lerman-Sagie T, Uyanik G, Weksberg R, Zirn B, Beaulieu CL, Majewski J, Bulman DE, O'Driscoll M, Shendure J, Graham JM, Jr., Boycott KM, Dobyns WB. De novo germline and postzygotic mutations in AKT3, PIK3R2 and PIK3CA cause a spectrum of related megalencephaly syndromes. Nat Genet 2012; 44: 934-40. PMID: 22729224; PMC_ID: 3408813.

Di Donato N, Jean YY, Maga AM, Krewson BD, Shupp AB, Avrutsky MI, Roy A, Collins S, Olds C, Willert RA, Czaja AM, Johnson R, Stover JA, Gottlieb S, Bartholdi D, Rauch A, Goldstein A, Boyd-Kyle V, Aldinger KA, Mirzaa GM, Nissen A, Brigatti KW, Puffenberger EG, Millen KJ, Strauss KA, Dobyns WB, Troy CM, Jinks RN. Mutations in CRADD Result in Reduced Caspase-2-Mediated Neuronal Apoptosis and Cause Megalencephaly with a Rare Lissencephaly Variant. Am J Hum Genet 2016; 99: 1117-1129. PMID 27773430 PMC5097945

Di Donato N, Timms AE, Aldinger KA, Mirzaa GM, Bennett JT, Collins S, Olds C, Mei D, Chiari S, Carvill G, Myers CT, Riviere JB, Zaki MS, University of Washington Center for Mendelian G, Gleeson JG, Rump A, Conti V, Parrini E, Ross ME, Ledbetter DH, Guerrini R, Dobyns WB. Analysis of 17 genes detects mutations in 81% of 811 patients with lissencephaly. Genet Med 2018; 20: 1354-1364. PMID 29671837 PMC6195491

Reiner O, Carrozzo R, Shen Y, Wehnert M, Faustinella F, Dobyns WB, Caskey CT, Ledbetter DH. Isolation of a Miller-Dieker lissencephaly gene containing G protein beta-subunit-like repeats. Nature 1993; 364: 717-21. PMID 8355785

Riviere JB, van Bon BW, Hoischen A, Kholmanskikh SS, O'Roak BJ, Gilissen C, Gijsen S, Sullivan CT, Christian SL, Abdul-Rahman OA, Atkin JF, Chassaing N, Drouin-Garraud V, Fry AE, Fryns JP, Gripp KW, Kempers M, Kleefstra T, Mancini GM, Nowaczyk MJ, van Ravenswaaij-Arts CM, Roscioli T, Marble M, Rosenfeld JA, Siu VM, de Vries BB, Shendure J, Verloes A, Veltman JA, Brunner HG, Ross ME, Pilz DT, Dobyns WB. De novo mutations in the actin genes ACTB and ACTG1 cause Baraitser-Winter syndrome. Nat Genet 2012; 44: 440-4, S1-2. PMID 22366783 PMC3677859

Aldinger KA, Lehmann OJ, Hudgins L, Chizhikov VV, Bassuk AG, Ades LC, Krantz ID, Dobyns WB, Millen KJ. FOXC1 is required for normal cerebellar development and is a major contributor to chromosome 6p25.3 Dandy-Walker malformation. Nat Genet 2009; 41: 1037-42. PMID 19668217 PMC2843139

Grinberg I, Northrup H, Ardinger H, Prasad C, Dobyns WB, Millen KJ. Heterozygous deletion of the linked genes ZIC1 and ZIC4 is involved in Dandy-Walker malformation. Nat Genet 2004; 36: 1053-5. PMID 15338008

Haldipur P, Aldinger KA, Bernardo S, Deng M, Timms AE, Overman LM, Winter C, Lisgo SN, Razavi F, Silvestri E, Manganaro L, Adle-Biasette H, Guilmiot F, Russo R, Kidron D, Hof PR, Gerrelli D, Lindsay SJ, Dobyns WB, Glass IA, Alexandre P, Millen KJ. Spatiotemporal expansion of primary progenitor zones in the developing human cerebellum. Science 2019; 366: 454-460. PMID 31624095

Najm J, Horn D, Wimplinger I, Golden JA, Chizhikov VV, Sudi J, Christian SL, Ullmann R, Kuechler A, Haas CA, Flubacher A, Charnas LR, Uyanik G, Frank U, Klopocki E, Dobyns WB, Kutsche K. Mutations of CASK cause an X-linked brain malformation phenotype with microcephaly and hypoplasia of the brainstem and cerebellum. Nat Genet 2008; 40: 1065-7. PMID 19165920

Alcantara D, Timms AE, Gripp K, Baker L, Park K, Collins S, Cheng C, Stewart F, Mehta SG, Saggar A, Sztriha L, Zombor M, Caluseriu O, Mesterman R, Van Allen MI, Jacquinet A, Ygberg S, Bernstein JA, Wenger AM, Guturu H, Bejerano G, Gomez-Ospina N, Lehman A, Alfei E, Pantaleoni C, Conti V, Guerrini R, Moog U, Graham JM, Jr., Hevner R, Dobyns WB, O'Driscoll M, Mirzaa GM. Mutations of AKT3 are associated with a wide spectrum of developmental disorders including extreme megalencephaly. Brain 2017; 140: 2610-2622. PMID 28969385 PMC6080423

Mirzaa GM, Parry DA, Fry AE, Giamanco KA, Schwartzentruber J, Vanstone M, Logan CV, Roberts N, Johnson CA, Singh S, Kholmanskikh SS, Adams C, Hodge RD, Hevner RF, Bonthron DT, Braun KP, Faivre L, Riviere JB, St-Onge J, Gripp KW, Mancini GM, Pang K, Sweeney E, van Esch H, Verbeek N, Wieczorek D, Steinraths M, Majewski J, Consortium FC, Boycott KM, Pilz DT, Ross ME, Dobyns WB, Sheridan EG. De novo CCND2 mutations leading to stabilization of cyclin D2 cause megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome. Nat Genet 2014; 46: 510-5. PMID 24705253 PMC4004933

Mirzaa GM, Conti V, Timms AE, Smyser CD, Ahmed S, Carter M, Barnett S, Hufnagel RB, Goldstein A, Narumi-Kishimoto Y, Olds C, Collins S, Johnston K, Deleuze JF, Nitschke P, Friend K, Harris C, Goetsch A, Martin B, Boyle EA, Parrini E, Mei D, Tattini L, Slavotinek A, Blair E, Barnett C, Shendure J, Chelly J, Dobyns WB, Guerrini R. Characterisation of mutations of the phosphoinositide-3-kinase regulatory subunit, PIK3R2, in perisylvian polymicrogyria: a next-generation sequencing study. Lancet Neurol 2015; 14: 1182-95. PMID 26520804 PMC4672724

Mirzaa GM, Campbell CD, Solovieff N, Goold CP, Jansen LA, Menon S, Timms AE, Conti V, Biag JD, Olds C, Boyle EA, Collins S, Ishak G, Poliachik SL, Girisha KM, Yeung KS, Chung BH, Rahikkala E, Gunter SA, McDaniel SS, Macmurdo CF, Bernstein JA, Martin B, Leary RJ, Mahan S, Liu S, Weaver M, Dorschner MO, Jhangiani S, Muzny DM, Boerwinkle E, Gibbs RA, Lupski JR, Shendure J, Saneto RP, Novotny EJ, Wilson CJ, Sellers WR, Morrissey MP, Hevner RF, Ojemann JG, Guerrini R, Murphy LO, Winckler W, Dobyns WB. Association of MTOR mutations with developmental brain disorders, including megalencephaly, focal cortical dysplasia, and pigmentary mosaicism. JAMA Neurol 2016; 73: 836-45. PMID 27159400 PMC4979321

Christian SL, Brune CW, Sudi J, Kumar RA, Liu S, Karamohamed S, Badner JA, Matsui S, Conroy J, McQuaid D, Gergel J, Hatchwell E, Gilliam TC, Gershon ES, Nowak NJ, Dobyns WB, Cook Jr EH. Novel submicroscopic chromosomal abnormalities detected in autism spectrum disorder. Biol Psychiatry 2008; 63: 1111-7, PMID 18374305 PMC2440346

Kortum F, Das S, Flindt M, Morris-Rosendahl DJ, Stefanova I, Goldstein A, Horn D, Klopocki E, Kluger G, Martin P, Rauch A, Roumer A, Saitta S, Walsh LE, Wieczorek D, Uyanik G, Kutsche K, Dobyns WB. The core FOXG1 syndrome phenotype consists of postnatal microcephaly, severe mental retardation, absent language, dyskinesia, and corpus callosum hypogenesis. J Med Genet 2011; 48: 396-406, PMID 21441262

Kumar RA, Karamohamed S, Sudi J, Conrad DF, Brune C, Badner JA, Gilliam TC, Nowak NJ, Cook EH, Jr., Dobyns WB, Christian SL. Recurrent 16p11.2 microdeletions in autism. Hum Mol Genet 2008; 17: 628-38. PMID 18156158

Stratton RF, Dobyns WB, Greenberg F, DeSana JB, Moore C, Fidone G, Runge GH, Feldman P, Sekhon GS, Pauli RM, et al. Interstitial deletion of (17)(p11.2p11.2): report of six additional patients with a new chromosome deletion syndrome. Am J Med Genet 1986; 24: 421-32. PMID 3728561