Dr. Heather C. Mefford, MD, PhD.

Dr. Heather Mefford member of KdVS Foundation Medical Advisory Board

Associate Professor of Pediatrics, University of Washington, Division of Genetic Medicine
Attending physician, Seattle Children’s Hospital, Genetic Medicine Clinic.

Contact Information

University of Washington
Department of Pediatrics
1959 NE Pacific St, Box 356320
Seattle, WA 98195
Email: [email protected]
Telephone Number: (206) 543-4748
Fax Number: (206) 543-3184


MD – University of Washington School of Medicine (2003)
PhD – University of Washington, Department of Genetics (2001) with Dr. Barbara Trask
Thesis: Evolution & biology of a subtelomeric repeat containing an expressed olfactory receptor gene
Residency – Department of Pediatrics, University of Washington, 2003-2006
Fellowship – Division of Medical Genetics, University of Washington, 2005-2008

Research Interests

Dr. Mefford’s research laboratory devoted to the discovery of novel genetic and genomic causes of pediatric disease. A major focus of their current work is to identify causes of pediatric epilepsy. To do this, they employ state-of-the-art technologies including whole exome sequencing, targeted gene panel sequencing and custom array comparative genomic hybridization (aCGH). The Mefford lab has discovered numerous new epilepsy genes and copy number variants. Dr. Mefford has also been involved in the discovery and characterization of several new genomic disorders, including deletions of chromosomes 1q21, 15q13 and 17q12, each of which cause a range of clinical features. She is continuing to investigate individuals with these conditions to better understand the variable outcomes. Dr. Mefford’s clinical interests parallel her research interests and include seeing patients with genomic disorders and patients with severe epilepsies and neurocognitive defects of unknown etiology.

Selected Publications

1: Myers CT, Mefford HC^ (2015) Advancing epilepsy genetics in the genomic era. Genome Medicine 7:91

2: Carvill GL, Crompton DE, Regan BM, McMahon JM, Saykally J, Zemel M, Schneider AL, Dibbens L, Howell KB, Mandelstam S, Leventer FJ, Harvey AS, Mullen SA, Berkovic SF, Sullivan J, Scheffer IE, Mefford HC^ (2015) Epileptic spasms are a feature of DEPDC5 mTORopathy. Neurology: Genetics (in press).

3: Jones K, Schwarze U, Adam M, Byers PH, Mefford HC^ (2015) A homozygous B3GAT3 mutation causes a severe syndrome with multiple fractures, expanding the phenotype of linkeropathy syndromes. Am J Med Gen doi:10.1002/ajmg.a.37209 [Epub ahead of print].

4: Bernier R, Steinman KJ, Reilly B, Wallace AS, Sherr EH, Pojman N, Mefford HC, Gerdts J, Earl R, Hanson E, Goin-Kochel RP, Berry L, Kanne S, Snyder LAG, Spence S, Ramocki MB, Evans DW, Spiro JE, Martin CL, Ledbetter DH, Chunk WK, Simons VIP Consortium (2015) Clinical phenotype of the recurrent 1q21.1 copy number variation. Genet Med doi: 10.1038/gim.2015.78 [epub ahead of print].

5: Carvill GL, McMahon JM, Schneider A, Zemel M, Myers CT, Saykally J, Nguyen J, Robbiano A, Zara F, Specchio N, Mecarelli O, Smith RL, Leventer RJ, Møller RS, Nikanorova M, Dimova P, Jordanova A, Petrou S, Euroepinomics RES, Helbig I, Striano P, Weckhuysen S, Berkovic SF, Scheffer IE, Mefford HC^. Mutations in the GABA transporter GAT-1 cause epilepsy with myoclonic astatic seizures. American Journal of Human Genetics 96:808-15.

6: van Bon BW, Coe BP, Bernier R, Green C, Gerdts J, Witherspoon K, Kleefstra T, Willemsen MH, Kumar R, Bosco P, Fichera M, Li D, Amaral D, Cristofoli F, Peeters H, Haan E, Romano C, Mefford HC, Scheffer I, Gecz J, de Vries BB, Eichler EE. Disruptive de novo mutations in DYRK1A lead to a syndromic form of autism and ID (2015) Mol Psych doi:10.1038/mp.2015.5 [Epub ahead of print].

7: Larsen J, Carvill GL, Gardella E, Kluger G, Schmiedel G, Barisic N, Depienne C, Brilstra E, Mang Y, Nielsen JEK, Kirkpatrick M, Goudie D, Goldman R, Jähn JA, Jepsen B, Gill D, Döcker M, Biskup S, McMahon JM, Koeleman B, Harris M, Braun K, de Kovel CGF, Marini C, Specchio N, Djémié T, Weckhuysen S, Tommerup N, Troncoso M, Troncoso L, EuroEPINOMICS RES CRP, Bevot A, Wolff M, Hjalgrim H, Guerrini R, Scheffer IE, Mefford HC^, Møller RS (2015) The phenotypic spectrum of SCN8A encephalopathy. Neurology 84:480-9.

8: EuroEPINOMICS-RES Consortium, Epilepsy Phenome/Genome Project, and Epi4K Consortium (2014) De novo mutations in synaptic transmission genes including DNM1 cause epileptic encephalopathies. Am J Hum Genet 95:360-70. PMCID PMC4185114.

9: Mefford HC^ (2014) CNVs in epilepsy. Current Genetic Medicine Reports. 2:162-7.

10: Bernier R, Golzio C, Xiong B, Stessman H, Coe BP, Penn O, Witherspoon K, Gerdts J, Baker C, Vulto-van Silfhout AT, Schuurs-Hoeijmakers JH, Fichera M, Bosco P, Buono S, Alberti A, Failla P, Peeters H, Steyaert J, Vissers LELM, Francescatto L, Mefford HC, Rosenfeld JA, Bakken T, O’Roak BJ, Pawlus M, Moon R, Shendure J, Amaral DG, Lein E, Rankin J, Romano C, de Vries BBA, Katsanis N, Eichler EE (2014) Disruptive CHD8 mutations define a subtype of autism early in development. Cell 158:263-76. PMCID: PMC4136921.

11: Reinthaler EM, Lal D, Lebon S, Hildebrand MS, Dahl HH, Regan BM, Feucht M, Steinböck H, Neophytou B, Ronen GM, Roche L, Gruber-Sedlmayr U, Geldner J, Haberlandt E, Hoffmann P, Herms S, Gieger C, Waldenberger M, Franke A, Wittig M, Schoch S, Becker AJ, Hahn A, Männik K, Toliat MR, Winterer G; The 16p11.2 European Consortium, Lerche H, Nürnberg P, Mefford H, Scheffer IE, Berkovic SF, Beckmann JS; The EPICURE Consortium; The EuroEPINOMICS Consortium, Sander T, Jacquemont S, Reymond A, Zimprich F, Neubauer BA (2014) 16p11.2 600 kb Duplications Confer Risk for Typical and Atypical Rolandic Epilepsy. Hum Mol Gen 23:6069-80.

12: Watson CT, Marques-Bonet T, Sharp AJ, Mefford HC^ (2014) The genetics of microdeletion and microduplication syndromes: an update. Annu Rev Genomics Hum Genet 15:215-44.

13: Carvill GL, Weckhuysen S, McMahon JM, Hartmann C, Moller RS, Hjalgrim H, Cook J, Geraghty E, O’Roak BJ, Petrou S, Clarke A, Gill D, Sadleir LG, Muhle H, von Spiczak S, Nikanorova M, Gazina EV, Suls A, Shendure J, De Jonghe P, Helbig I, Berkovic SF, Scheffer IE, Mefford HC^ (2013) GABRA1 and STXBP1: novel genetic causes of Dravet syndrome. Neurology

14: Mullen SA#, Carvill GL#, Bellows S, Bayly MA, Trucks H, Lal D, Sander T, Berkovic SF, Dibbens LM, Scheffer IE, Mefford HC^ (2013) Copy number variants are frequent in genetic generalized epilepsy with intellectual disability. Neurology 81:1507-14.

15: Carvill GL, Regan BM, Yendle SC, O’Roak BJ, Lozovaya N, Bruneau N, Burnashev N, Khan A, Cook J, Sadleir LG, Turner SJ, Tsai MH, Webster R, Ouvrier R, Damiano J, Berkovic SF, Shendure J, Hildebrand M, Szepetowski P, Scheffer IE, Mefford HC^ (2013) GRIN2A mutations cause epilepsy-aphasia spectrum disorders. Nature Genetics 45:1073-6. PMCID: PMC3868952.

16: Epi4K Consortium; Epilepsy Phenome/Genome Project. (2013) De novo mutation in epileptic encephalopathies. Nature 501:217-21. PMCID: PMC3773011.

17: Carvill GL, Heavin SB, Yendle SC, McMahon JM, O’Roak BJ, Cook J, Khan A, Dorschner MO, Weaver M, Calvery S, Malone S, Wallace G, Stanley T, Bye AME, Bleasel A, Howell KB, Kivity S, Mackey MT, Rodriguez-Casero V, Webster R, Korczyn A, Afawi Z, Zelnick N, Lerman-Sagie T, Lev D, Møller RS, Gill D, Andrade DM, Freeman JL, Sadleir LG, Shendure J, Berkovic SF, Scheffer IE, Mefford HC^ (2013) Targeted resequencing in epileptic encephalopathies reveals marked genetic heterogeneity and novel genes including CHD2 and SYNGAP1. Nature Genetics 45:825-30. PMCID: PMC3704157.

18: Carvill GL, Mefford HC^ (2013) Microdeletion syndromes. Curr Opin Genet Dev 23:232-9.

19: O’Roak BJ, Vives L, Fu W, Egertson JD, Stanaway IB, Phelps IG, Carvill GL, Kumar K, Lee C, Ankenman K, Munson J, Hiatt JB, Turner EH, Levy R, O’Day DR, Krumm N, Coe BP, Martin BK, Borenstein E, Nickerson DA, Mefford HC, Doherty D, Akey JM, Bernier R, Eichler EE, Shendure J (2012) Massively multiplex targeted sequencing identified genes recurrently disrupted in autism spectrum disorders. Science 338:1619-22. PMCID: PMC3528801.

20: Mefford HC^, Batshaw ML, Hoffman EP (2012) Genomics, Intellectual Disability and Autism. New England Journal of Medicine 366:733-43.

21: Mefford HC, Shur N, Rosenfeld J (2012) 15q24 Microdeletion. In GeneReviews at GeneTests: Medical Genetics Information Resource. Copyright, University of Washington, Seattle, 1997-2011. Available at http://www.genetests.org.

22: Mefford HC^, Rosenfeld JA, Shur N, Slavotinek AM, Cox VA, Hennekam RC, Firth HV, Willatt L, Wheeler P, Morrow EM, Cook J, Sullivan R, Oh A, McDonald MT, Zonana J, Keller K, Hannibal MC, Ball S, Kussmann J, Gorski J, Zelewski S, Banks V, Smith W, Smith R, Paull L, Rosenbaum KN, Amor DJ, Silva J, Lamb A, Eichler EE (2011) Further clinical and molecular delineation of the 15q24 microdeletion syndrome. J Med Genet 49:110-8. PMCID: PMC3261729

23: *Mefford HC^, Yendle SC, Hsu C, Cook J, Geraghty E, McMahon JM, Eeg-Olofsson O, Sadleir LG, Gill D, Ben-Zeev B, Lerman-Sagie T, Mackay M, Freeman JL, Andermann E, Pelakanos J, Andrews I, Wallace G, Eichler EE, Berkovic SF, Scheffer IE (2011) Rare copy number variants are an important cause of epileptic encephalopathies. Annals of Neurology 70:974-85. PMCID: PMC3245646

24: van Bon BWM, Mefford HC, de Vries BBA (2010) 15q13.3 Microdeletion. In GeneReviews at GeneTests: Medical Genetics Information Resource (http://www.genetests.org). Copyright University of Washington, Seattle. 1997-2011.

25: Bachmann-Gagescu R*, Mefford HC*^, Cowan C, Glew GM, Hing AV, Wallace S, Bader PI, Hamati A, Reitnauer PJ, Smith R, Stockton SW, Muhle H, Helbig I, Eichler EE, Ballif BC, Rosenfeld J, Tsuchiya KD (2010) Recurrent 200-kb deletions of 16p11.2 that include the SH2B1 gene are associated with developmental delay and obesity. Genetics in Medicine 12:641-7

26: Mefford HC^, Muhle H, Ostertag P, von Spiczak S, Buysse K, Baker C, Franke A, Malafosse A, Genton P, Thomas P, Gurnett CA, Schreiber S, Bassuk AG, Guipponi M, Stephani U, Helbig I, Eichler EE. (2010) Genome-wide copy number variation in epilepsy: novel susceptibility loci in idiopathic generalized and focal epilepsies. PLoS Genetics 6:e1000962. PMCID: PMC2873910.

27: Mefford HC. (2009) Genotype to phenotype discovery and characterization of novel genomic disorders in a genotype-first era. Genetics in Medicine 11:836-42.

28: Mefford HC, Cooper GM, Zerr T, Smith J, Baker C, Shafer N, Thorland E, Skinner C, Schwartz CE, Nickerson DA, Eichler EE (2009) A high-throughput and cost-effective method for CNV genotyping Genome Research 19:1579-85.

29: Mefford HC, Eichler EE (2009) Duplication Hotspots, Rare Genomic Disorders and Common Disease. Current Opinion in Genetics & Development 19:196-204.

30: van Bon BWM, Mefford HC, Menten B, Koolen DA, Sharp AJ, Nillesen WM, Innis JW, de Ravel TJL, Mercer C, Fichera M, Stewart H, Connell LE, Ounap K, Castle B, et al. (2009) Further delineation of the 15q13 micro-deletion and duplication syndrome: A clinical spectrum varying from non-pathogenic to a severe outcome. Journal of Medical Genetics 46:511-23.

31: Helbig I, Mefford HC, Sharp AJ, Guipponi M, Fichera M, Franke A, Muhle H, de Kovel C, Baker C, von Spiczak S, Kron KL, Steinich I, Kleefuß-Lie AA, Leu C, Gaus V, Schmitz B, Klein KM, Reif PS, Rosenow F, Weber Y, Lerche H, Zimprich F, Urak L, Fuchs K, Feucht M, Genton P, Thomas P, Visscher F, de Haan G, Møller RS, Hjalgrim H, Luciano D, Wittig M, Nothnagel M, Elger CE, Nuernberg P, Romano C, Malafosse A, Koeleman BPC, Lindhout D, Stephani U, Schreiber D, Eichler EE, Sander T (2009) 15q13.3 microdeletions increase risk of idiopathic generalized epilepsy. Nature Genetics 41:160-2.

32: Mefford HC, Sharp AJ, Baker C, Itsara A, Jiang Z, Buysse K, Huang S, Maloney VK, Crolla JA, Baralle D, Collins A, Mercer C, Norga K, de Ravel T, et al. (2008) Recurrent rearrangements of chromosome 1q21.1 and variable pediatric phenotypes. New England Journal of Medicine 359: 1685-99.

33: Sharp AJ, Mefford HC, Li KE, Broomer AJ, Wang Y, Xiao C, Barbacioru C, Baker C, Skinner C, Stevenson RE, Schroer R, Novara F, De Gregori M, Ciccone R, Gimelli G, Bernardina BD, Torniero C, Giorda R, Regan R, Murday V, Mansour S, Fichera M, Castiglia L, Failla P, Cooper GM, Knight SJL, Romano C, Zuffardi O, Chen C, Schwartz C, Eichler EE (2008) A recurrent 15q13.3 microdeletion syndrome associated with mental retardation and seizures. Nature Genetics 40:322-8.

34: Hannes F, Sharp AJ, Mefford HC, de Ravel T, Ruivenkamp CA, Breuning MH, Fryns J-P, Devriendt K, Van Buggenhout G, Vogels A, Stewart H, Hennekam RC, Cooper GM, Regan R, Knight JSL, Eichler EE, Vermeesch JR. (2009) Recurrent reciprocal deletions and duplications of 16p13.11: The deletion is a risk factor for MR/MCA while the duplication may be a rare benign variant. Journal of Medical Genetics 46:223-32 [Epub 2008 Jun 11].

35: Mefford HC, Clauin S, Sharp AJ, Moller RS, Ullman R, Kapur R, Pinkel D, Cooper GM, Ropers HH, Tommerup N, Eichler EE, Bellanne-Chantelot C. (2007) Recurrent reciprocal genomic rearrangements of 17q12 are involved in renal disease, diabetes and epilepsy. American Journal of Human Genetics 81:1057-69.

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