title: Gene discovery for Mendelian conditions via social networking: de novo variants in KDM1A cause developmental delay and distinctive facial features.
abstract: The pace of Mendelian gene discovery is slowed by the "n-of-1 problem"-the difficulty of establishing the causality of a putatively pathogenic variant in a single person or family. Identification of an unrelated person with an overlapping phenotype and suspected pathogenic variant in the same gene can overcome this barrier, but it is often impeded by lack of a convenient or widely available way to share data on candidate variants/genes among families, clinicians, and researchers.
  
  
  
  Social networking among families, clinicians, and researchers was used to identify three children with variants of unknown significance in KDM1A and similar phenotypes.
  
  
  
  De novo variants in KDM1A underlie a new syndrome characterized by developmental delay and distinctive facial features.
  
  
  
  Social networking is a potentially powerful strategy to discover genes for rare Mendelian conditions, particularly those with nonspecific phenotypic features. To facilitate the efforts of families to share phenotypic and genomic information with each other, clinicians, and researchers, we developed the Repository for Mendelian Genomics Family Portal (RMD-FP; http://uwcmg.org/#/family). Design and development of MyGene2 (http://www.mygene2.org), a Web-based tool that enables families, clinicians, and researchers to search for gene matches based on analysis of phenotype and exome data deposited into the RMD-FP, is under way.Genet Med 18 8, 788-795.
authors.affiliation: Department of Pediatrics, University of Washington, Seattle, Washington, USA.
authors.forename: Jessica X
authors.identifier: 0000-0002-1616-2448
authors.initials: JX
authors.lastname: Chong
authors.affiliation: Department of Pediatrics, University of Washington, Seattle, Washington, USA.
authors.forename: Joon-Ho
authors.initials: JH
authors.lastname: Yu
authors.affiliation: Department of Political Science, University of California, Berkeley, California, USA.
authors.forename: Peter
authors.identifier: 0000-0001-6354-795X
authors.initials: P
authors.lastname: Lorentzen
authors.affiliation: Citizen scientist, San Francisco, California, USA.
authors.forename: Karen M
authors.identifier: 0000-0002-3433-0601
authors.initials: KM
authors.lastname: Park
authors.affiliation: Department of Pediatrics, University of Washington, Seattle, Washington, USA.
authors.forename: Seema M
authors.initials: SM
authors.lastname: Jamal
authors.affiliation: Department of Pediatrics, University of Washington, Seattle, Washington, USA.|Treuman Katz Center for Pediatric Bioethics, Seattle Children's Research Institute, Seattle, Washington, USA.|Department of Genome Sciences, University of Washington, Seattle, Washington, USA.
authors.forename: Holly K
authors.identifier: 0000-0003-1005-5008
authors.initials: HK
authors.lastname: Tabor
authors.affiliation: Institute for Medical Genetics, University of Zurich, Zurich, Switzerland.
authors.forename: Anita
authors.initials: A
authors.lastname: Rauch
authors.affiliation: Department of Pediatrics, University of Colorado, Aurora, Colorado, USA.
authors.forename: Margarita Sifuentes
authors.identifier: 0000-0002-8782-8059
authors.initials: MS
authors.lastname: Saenz
authors.affiliation: Department of Neurology, Children's Hospital of the University of Zurich, Zurich, Switzerland.
authors.forename: Eugen
authors.initials: E
authors.lastname: Boltshauser
authors.affiliation: Department of Genome Sciences, University of Washington, Seattle, Washington, USA.
authors.forename: Karynne E
authors.initials: KE
authors.lastname: Patterson
authors.affiliation: Department of Genome Sciences, University of Washington, Seattle, Washington, USA.
authors.forename: Deborah A
authors.initials: DA
authors.lastname: Nickerson
authors.affiliation: Department of Pediatrics, University of Washington, Seattle, Washington, USA.|Department of Genome Sciences, University of Washington, Seattle, Washington, USA.|Division of Genetic Medicine, Seattle Children's Hospital, Seattle, Washington, USA.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Bamshad
mesh_terms: D002648:Child; D002675:Child, Preschool; D016208:Databases, Factual; D002658:Developmental Disabilities / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies / Q000379:methods*; D056466:Histone Demethylases / Q000235:genetics*; D006801:Humans; D033181:Information Dissemination; D008297:Male; D020125:Mutation, Missense; D010641:Phenotype; D060756:Social Networking; D064878:Web Browser
chemical_list: D056466:Histone Demethylases; C495195:KDM1A protein, human