title: X-exome sequencing of 405 unresolved families identifies seven novel intellectual disability genes.
abstract: X-linked intellectual disability (XLID) is a clinically and genetically heterogeneous disorder. During the past two decades in excess of 100 X-chromosome ID genes have been identified. Yet, a large number of families mapping to the X-chromosome remained unresolved suggesting that more XLID genes or loci are yet to be identified. Here, we have investigated 405 unresolved families with XLID. We employed massively parallel sequencing of all X-chromosome exons in the index males. The majority of these males were previously tested negative for copy number variations and for mutations in a subset of known XLID genes by Sanger sequencing. In total, 745 X-chromosomal genes were screened. After stringent filtering, a total of 1297 non-recurrent exonic variants remained for prioritization. Co-segregation analysis of potential clinically relevant changes revealed that 80 families (20%) carried pathogenic variants in established XLID genes. In 19 families, we detected likely causative protein truncating and missense variants in 7 novel and validated XLID genes (CLCN4, CNKSR2, FRMPD4, KLHL15, LAS1L, RLIM and USP27X) and potentially deleterious variants in 2 novel candidate XLID genes (CDK16 and TAF1). We show that the CLCN4 and CNKSR2 variants impair protein functions as indicated by electrophysiological studies and altered differentiation of cultured primary neurons from Clcn4(-/-) mice or after mRNA knock-down. The newly identified and candidate XLID proteins belong to pathways and networks with established roles in cognitive function and intellectual disability in particular. We suggest that systematic sequencing of all X-chromosomal genes in a cohort of patients with genetic evidence for X-chromosome locus involvement may resolve up to 58% of Fragile X-negative cases.
authors: Department of Human Molecular Genetics, Max Planck Institute for Molecular Genetics, Berlin, Germany.
authors: H
authors: H
authors: Hu
authors: Department of Computational Molecular Biology, Max Planck Institute for Molecular Genetics, Berlin, Germany.
authors: S A
authors: SA
authors: Haas
authors: University Paris Descartes, Paris, France.|Centre National de la Recherche Scientifique Unité Mixte de Recherche 8104, Institut National de la Santé et de la Recherche Médicale Unité 1016, Institut Cochin, Paris, France.
authors: J
authors: J
authors: Chelly
authors: Center for Human Genetics, University Hospitals Leuven, Leuven, Belgium.
authors: H
authors: H
authors: Van Esch
authors: Inserm U930 'Imaging and Brain', Tours, France.|University François-Rabelais, Tours, France.|Centre Hospitalier Régional Universitaire, Service de Génétique, Tours, France.
authors: M
authors: M
authors: Raynaud
authors: Department of Human Genetics, Radboud University Medical Center, Donders Institute for Brain, Cognition and Behaviour, Nijmegen, The Netherlands.
authors: A P M
authors: AP
authors: de Brouwer
authors: Max-Delbrück-Centrum für Molekulare Medizin, Berlin, Germany.|Leibniz-Institut für Molekulare Pharmakologie, Berlin, Germany.
authors: S
authors: S
authors: Weinert
authors: Human Genome Laboratory, VIB Center for the Biology of Disease, Leuven, Belgium.|Human Genome Laboratory, Department of Human Genetics, K.U. Leuven, Leuven, Belgium.
authors: G
authors: G
authors: Froyen
authors: Department of Clinical Genetics, Maastricht University Medical Center, azM, Maastricht, The Netherlands.|School for Oncology and Developmental Biology, GROW, Maastricht University, Maastricht, The Netherlands.
authors: S G M
authors: SG
authors: Frints
authors: Inserm U930 'Imaging and Brain', Tours, France.|University François-Rabelais, Tours, France.
authors: F
authors: F
authors: Laumonnier
authors: Department of Computational Molecular Biology, Max Planck Institute for Molecular Genetics, Berlin, Germany.
authors: T
authors: T
authors: Zemojtel
authors: Department of Computational Molecular Biology, Max Planck Institute for Molecular Genetics, Berlin, Germany.
authors: M I
authors: MI
authors: Love
authors: Department of Computational Molecular Biology, Max Planck Institute for Molecular Genetics, Berlin, Germany.
authors: H
authors: H
authors: Richard
authors: Department of Computational Molecular Biology, Max Planck Institute for Molecular Genetics, Berlin, Germany.
authors: A-K
authors: AK
authors: Emde
authors: Department of Human Molecular Genetics, Max Planck Institute for Molecular Genetics, Berlin, Germany.
authors: M
authors: M
authors: Bienek
authors: Department of Human Molecular Genetics, Max Planck Institute for Molecular Genetics, Berlin, Germany.
authors: C
authors: C
authors: Jensen
authors: Department of Human Molecular Genetics, Max Planck Institute for Molecular Genetics, Berlin, Germany.
authors: M
authors: M
authors: Hambrock
authors: Department of Human Molecular Genetics, Max Planck Institute for Molecular Genetics, Berlin, Germany.
authors: U
authors: U
authors: Fischer
authors: Max-Delbrück-Centrum für Molekulare Medizin, Berlin, Germany.
authors: C
authors: C
authors: Langnick
authors: Max-Delbrück-Centrum für Molekulare Medizin, Berlin, Germany.
authors: M
authors: M
authors: Feldkamp
authors: Department of Human Genetics, Radboud University Medical Center, Donders Institute for Brain, Cognition and Behaviour, Nijmegen, The Netherlands.
authors: W
authors: W
authors: Wissink-Lindhout
authors: University Paris Descartes, Paris, France.|Centre National de la Recherche Scientifique Unité Mixte de Recherche 8104, Institut National de la Santé et de la Recherche Médicale Unité 1016, Institut Cochin, Paris, France.
authors: N
authors: N
authors: Lebrun
authors: University Paris Descartes, Paris, France.|Centre National de la Recherche Scientifique Unité Mixte de Recherche 8104, Institut National de la Santé et de la Recherche Médicale Unité 1016, Institut Cochin, Paris, France.
authors: L
authors: L
authors: Castelnau
authors: University Paris Descartes, Paris, France.|Centre National de la Recherche Scientifique Unité Mixte de Recherche 8104, Institut National de la Santé et de la Recherche Médicale Unité 1016, Institut Cochin, Paris, France.
authors: J
authors: J
authors: Rucci
authors: University Paris Descartes, Paris, France.|Centre National de la Recherche Scientifique Unité Mixte de Recherche 8104, Institut National de la Santé et de la Recherche Médicale Unité 1016, Institut Cochin, Paris, France.
authors: R
authors: R
authors: Montjean
authors: University Paris Descartes, Paris, France.|Centre National de la Recherche Scientifique Unité Mixte de Recherche 8104, Institut National de la Santé et de la Recherche Médicale Unité 1016, Institut Cochin, Paris, France.
authors: O
authors: O
authors: Dorseuil
authors: University Paris Descartes, Paris, France.|Centre National de la Recherche Scientifique Unité Mixte de Recherche 8104, Institut National de la Santé et de la Recherche Médicale Unité 1016, Institut Cochin, Paris, France.
authors: P
authors: P
authors: Billuart
authors: Max-Delbrück-Centrum für Molekulare Medizin, Berlin, Germany.|Leibniz-Institut für Molekulare Pharmakologie, Berlin, Germany.
authors: T
authors: T
authors: Stuhlmann
authors: School of Paediatrics and Reproductive Health, The University of Adelaide, Adelaide, SA, Australia.|Robinson Research Institute, The University of Adelaide, Adelaide, SA, Australia.
authors: M
authors: M
authors: Shaw
authors: School of Paediatrics and Reproductive Health, The University of Adelaide, Adelaide, SA, Australia.|Robinson Research Institute, The University of Adelaide, Adelaide, SA, Australia.
authors: M A
authors: MA
authors: Corbett
authors: School of Paediatrics and Reproductive Health, The University of Adelaide, Adelaide, SA, Australia.|Robinson Research Institute, The University of Adelaide, Adelaide, SA, Australia.
authors: A
authors: A
authors: Gardner
authors: School of Paediatrics and Reproductive Health, The University of Adelaide, Adelaide, SA, Australia.|National Heart and Lung Institute, Imperial College London, London, UK.
authors: S
authors: S
authors: Willis-Owen
authors: School of Paediatrics and Reproductive Health, The University of Adelaide, Adelaide, SA, Australia.
authors: C
authors: C
authors: Tan
authors: SA Pathology, Women's and Children's Hospital, Adelaide, SA, Australia.
authors: K L
authors: KL
authors: Friend
authors: Human Genome Laboratory, VIB Center for the Biology of Disease, Leuven, Belgium.|Human Genome Laboratory, Department of Human Genetics, K.U. Leuven, Leuven, Belgium.
authors: S
authors: S
authors: Belet
authors: Department of Clinical Genetics, Maastricht University Medical Center, azM, Maastricht, The Netherlands.|School for Oncology and Developmental Biology, GROW, Maastricht University, Maastricht, The Netherlands.
authors: K E P
authors: KE
authors: van Roozendaal
authors: Centre Hospitalier Régional Universitaire, Service de Génétique, Tours, France.
authors: M
authors: M
authors: Jimenez-Pocquet
authors: Inserm U930 'Imaging and Brain', Tours, France.|University François-Rabelais, Tours, France.|Centre Hospitalier Régional Universitaire, Service de Génétique, Tours, France.
authors: M-P
authors: MP
authors: Moizard
authors: Inserm U930 'Imaging and Brain', Tours, France.|University François-Rabelais, Tours, France.|Centre Hospitalier Régional Universitaire, Service de Génétique, Tours, France.
authors: N
authors: N
authors: Ronce
authors: Department of Computational Molecular Biology, Max Planck Institute for Molecular Genetics, Berlin, Germany.
authors: R
authors: R
authors: Sun
authors: Department of Computational Molecular Biology, Max Planck Institute for Molecular Genetics, Berlin, Germany.
authors: S
authors: S
authors: O'Keeffe
authors: Department of Computational Molecular Biology, Max Planck Institute for Molecular Genetics, Berlin, Germany.
authors: R
authors: R
authors: Chenna
authors: Department of Computational Molecular Biology, Max Planck Institute for Molecular Genetics, Berlin, Germany.
authors: A
authors: A
authors: van Bömmel
authors: Department of Computational Molecular Biology, Max Planck Institute for Molecular Genetics, Berlin, Germany.
authors: J
authors: J
authors: Göke
authors: Genetics of Learning and Disability Service, Hunter Genetics, Waratah, NSW, Australia.
authors: A
authors: A
authors: Hackett
authors: Genetics of Learning and Disability Service, Hunter Genetics, Waratah, NSW, Australia.
authors: M
authors: M
authors: Field
authors: Genetics of Learning and Disability Service, Hunter Genetics, Waratah, NSW, Australia.
authors: L
authors: L
authors: Christie
authors: Genetics of Learning and Disability Service, Hunter Genetics, Waratah, NSW, Australia.
authors: J
authors: J
authors: Boyle
authors: School of Paediatrics and Reproductive Health, The University of Adelaide, Adelaide, SA, Australia.|SA Pathology, Women's and Children's Hospital, Adelaide, SA, Australia.
authors: E
authors: E
authors: Haan
authors: Genetic Services of Western Australia, King Edward Memorial Hospital, Perth, WA, Australia.
authors: J
authors: J
authors: Nelson
authors: Genetics of Learning and Disability Service, Hunter Genetics, Waratah, NSW, Australia.
authors: G
authors: G
authors: Turner
authors: Genetic Services of Western Australia, King Edward Memorial Hospital, Perth, WA, Australia.|School of Paediatrics and Child Health, University of Western Australia, Perth, WA, Australia.|Institute for Immunology and Infectious Diseases, Murdoch University, Perth, WA, Australia.|Telethon Kids Institute, Perth, WA, Australia.
authors: G
authors: G
authors: Baynam
authors: Institut für Humangenetik, Universität zu Lübeck, Lübeck, Germany.
authors: G
authors: G
authors: Gillessen-Kaesbach
authors: Institut für Humangenetik, Justus-Liebig-Universität Giessen, Giessen, Germany.|bio.logis Center for Human Genetics, Frankfurt a. M., Germany.
authors: U
authors: U
authors: Müller
authors: Institut für Humangenetik, Justus-Liebig-Universität Giessen, Giessen, Germany.|bio.logis Center for Human Genetics, Frankfurt a. M., Germany.
authors: D
authors: D
authors: Steinberger
authors: Chair and Department of Endocrinology, Metabolism and Internal Diseases, Ponzan University of Medical Sciences, Poznan, Poland.
authors: B
authors: B
authors: Budny
authors: Chair and Department of Medical Genetics, Poznan University of Medical Sciences, Poznan, Poland.
authors: M
authors: M
authors: Badura-Stronka
authors: Chair and Department of Medical Genetics, Poznan University of Medical Sciences, Poznan, Poland.
authors: A
authors: A
authors: Latos-Bieleńska
authors: Department of Clinical Genetics, Odense University Hospital, Odense, Denmark.
authors: L B
authors: LB
authors: Ousager
authors: Institut für Humangenetik, Universitätsklinikum Münster, Muenster, Germany.
authors: P
authors: P
authors: Wieacker
authors: Unidad de Genética Clínica, Hospital Virgen del Rocío, Sevilla, España.
authors: G
authors: G
authors: Rodríguez Criado
authors: Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.
authors: M-L
authors: ML
authors: Bondeson
authors: Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.
authors: G
authors: G
authors: Annerén
authors: Institut für Medizinische Genetik und Angewandte Genomik, Tübingen, Germany.
authors: A
authors: A
authors: Dufke
authors: Kinderzentrum München, München, Germany.
authors: M
authors: M
authors: Cohen
authors: Centre de Génétique Humaine, Université de Franche-Comté, Besançon, France.
authors: L
authors: L
authors: Van Maldergem
authors: Service de Génétique, Hôpital Jeanne de Flandre CHRU de Lilles, Lille, France.
authors: C
authors: C
authors: Vincent-Delorme
authors: Service de Neuro-Pédiatrie, CHU Montpellier, Montpellier, France.
authors: B
authors: B
authors: Echenne
authors: Laboratoire SESEP, Centre hospitalier de Versailles, Le Chesnay, France.
authors: B
authors: B
authors: Simon-Bouy
authors: Department of Human Genetics, Radboud University Medical Center, Donders Institute for Brain, Cognition and Behaviour, Nijmegen, The Netherlands.
authors: T
authors: T
authors: Kleefstra
authors: Department of Human Genetics, Radboud University Medical Center, Donders Institute for Brain, Cognition and Behaviour, Nijmegen, The Netherlands.
authors: M
authors: M
authors: Willemsen
authors: Center for Human Genetics, University Hospitals Leuven, Leuven, Belgium.
authors: J-P
authors: JP
authors: Fryns
authors: Center for Human Genetics, University Hospitals Leuven, Leuven, Belgium.
authors: K
authors: K
authors: Devriendt
authors: Department of Human Molecular Genetics, Max Planck Institute for Molecular Genetics, Berlin, Germany.
authors: R
authors: R
authors: Ullmann
authors: Department of Computational Molecular Biology, Max Planck Institute for Molecular Genetics, Berlin, Germany.
authors: M
authors: M
authors: Vingron
authors: Department of Human Molecular Genetics, Max Planck Institute for Molecular Genetics, Berlin, Germany.|Department of Biochemistry and Medical Genetics, University of Manitoba, Winnipeg, MB, Canada.
authors: K
authors: K
authors: Wrogemann
authors: Department of Human Molecular Genetics, Max Planck Institute for Molecular Genetics, Berlin, Germany.
authors: T F
authors: TF
authors: Wienker
authors: Department of Human Molecular Genetics, Max Planck Institute for Molecular Genetics, Berlin, Germany.
authors: A
authors: A
authors: Tzschach
authors: Department of Human Genetics, Radboud University Medical Center, Donders Institute for Brain, Cognition and Behaviour, Nijmegen, The Netherlands.
authors: H
authors: H
authors: van Bokhoven
authors: School of Paediatrics and Reproductive Health, The University of Adelaide, Adelaide, SA, Australia.|Robinson Research Institute, The University of Adelaide, Adelaide, SA, Australia.
authors: J
authors: http://orcid.org/0000-0002-7884-6861
authors: J
authors: Gecz
authors: Max-Delbrück-Centrum für Molekulare Medizin, Berlin, Germany.|Leibniz-Institut für Molekulare Pharmakologie, Berlin, Germany.
authors: T J
authors: TJ
authors: Jentsch
authors: Department of Human Molecular Genetics, Max Planck Institute for Molecular Genetics, Berlin, Germany.|Max-Delbrück-Centrum für Molekulare Medizin, Berlin, Germany.
authors: W
authors: W
authors: Chen
authors: Department of Human Molecular Genetics, Max Planck Institute for Molecular Genetics, Berlin, Germany.
authors: H-H
authors: HH
authors: Ropers
authors: Department of Human Molecular Genetics, Max Planck Institute for Molecular Genetics, Berlin, Germany.
authors: V M
authors: VM
authors: Kalscheuer
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics; D000293:Adolescent; D000328:Adult; D000818:Animals; D002478:Cells, Cultured; D018118:Chloride Channels / Q000235:genetics / Q000378:metabolism; D015331:Cohort Studies; D018844:Cyclin-Dependent Kinases / Q000235:genetics; D014644:Genetic Variation; D059014:High-Throughput Nucleotide Sequencing; D051548:Histone Acetyltransferases / Q000235:genetics; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics; D008297:Male; D038901:X-Linked Intellectual Disability / Q000235:genetics*; D018345:Mice, Knockout; D008840:Microfilament Proteins / Q000235:genetics; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D009687:Nuclear Proteins / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D035381:TATA-Binding Protein Associated Factors / Q000235:genetics; D035362:Transcription Factor TFIID / Q000235:genetics; D044767:Ubiquitin-Protein Ligases / Q000235:genetics
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C097503:CLC-5 chloride channel; C484312:CLCN4 protein, human; C479421:CNKSR2 protein, human; D018118:Chloride Channels; C539678:FRMPD4 protein, human; D047908:Intracellular Signaling Peptides and Proteins; C503716:KLHL15 protein, human; C552426:Las1L protein, human; D008840:Microfilament Proteins; D009687:Nuclear Proteins; D012333:RNA, Messenger; D035381:TATA-Binding Protein Associated Factors; D035362:Transcription Factor TFIID; D051548:Histone Acetyltransferases; C492370:RLIM protein, human; D044767:Ubiquitin-Protein Ligases; C069001:TATA-binding protein associated factor 250 kDa; D018844:Cyclin-Dependent Kinases; C089463:PCTAIRE-1 protein kinase
references: J Med Genet. 2007 Jul;44(7):472-7
references: 17369503
references: Stat Appl Genet Mol Biol. 2011 Nov 08;10(1):null
references: 23089826
references: Nat Genet. 2011 Jun;43(6):585-9
references: 21572417
references: Mol Psychiatry. 2012 Jan;17(1):4-7
references: 21826058
references: J Hum Genet. 2010 Apr;55(4):244-7
references: 20339384
references: Bioinformatics. 2009 Aug 1;25(15):1966-7
references: 19497933
references: Genome Res. 2008 Nov;18(11):1851-8
references: 18714091
references: J Biol Chem. 1999 May 7;274(19):13462-9
references: 10224112
references: Am J Hum Genet. 2013 Sep 5;93(3):579-86
references: 24011989
references: Cell. 2001 Jan 26;104(2):205-15
references: 11207362
references: Genes Cells. 2002 Nov;7(11):1149-60
references: 12390249
references: Nat Genet. 2007 Apr;39(4):451-3
references: 17334363
references: Eur J Neurosci. 2012 Jul;36(1):1960-70
references: 22595022
references: Mol Cell. 2009 Apr 24;34(2):145-54
references: 19394292
references: Nature. 2012 Sep 13;489(7415):313-7
references: 22885700
references: Science. 2012 Feb 17;335(6070):823-8
references: 22344438
references: J Am Chem Soc. 2006 May 3;128(17):5913-22
references: 16637659
references: Mol Cell. 2008 Jan 18;29(1):92-101
references: 18206972
references: J Biol Chem. 1999 Apr 23;274(17 ):11889-96
references: 10207009
references: Nature. 2012 Apr 04;485(7397):237-41
references: 22495306
references: J Physiol. 2004 Jun 1;557(Pt 2):363-78
references: 14724190
references: Am J Med Genet A. 2013 Dec;161A(12):3063-71
references: 24039113
references: Nat Genet. 2002 Apr;30(4):436-40
references: 11889465
references: Hum Mutat. 2014 Jan;35(1):41-4
references: 24115387
references: J Med Genet. 2012 Aug;49(8):539-43
references: 22889856
references: J Biol Chem. 2010 Nov 5;285(45):34537-48
references: 20817731
references: Ann Neurol. 2014 Nov;76(5):758-64
references: 25223753
references: Neuroscience. 2011 Apr 28;180:353-9
references: 21335063
references: J Biol Chem. 2006 Apr 14;281(15):9852-8
references: 16461345
references: Cell. 2009 Jul 23;138(2):389-403
references: 19615732
references: Lancet Neurol. 2013 Jul;12(7):659-68
references: 23707145
references: Genome Res. 2009 Sep;19(9):1646-54
references: 19592482
references: J Med Genet. 2003 Jan;40(1):11-7
references: 12525535
references: Nature. 2005 Jul 21;436(7049):424-7
references: 16034422
references: Orphanet J Rare Dis. 2014 Apr 11;9:49
references: 24721225
references: J Biol Chem. 2010 Jun 4;285(23):17595-603
references: 20351103
references: BMC Bioinformatics. 2010 Nov 08;11:548
references: 21059217
references: Am J Med Genet A. 2014 Mar;164A(3):789-95
references: 24357419
references: Am J Hum Genet. 2012 Oct 5;91(4):694-702
references: 23000143
references: Nat Cell Biol. 2003 Nov;5(11):1001-7
references: 14528312
references: Genes Dev. 2009 Jun 1;23(11):1289-302
references: 19487570
references: Cell Growth Differ. 1999 Mar;10(3):173-81
references: 10099831
references: Genome Res. 2009 Oct;19(10 ):1905-11
references: 19549727
references: Cell. 2010 May 28;141(5):846-58
references: 20510931
references: Am J Hum Genet. 2012 Feb 10;90(2):295-300
references: 22305531
references: J Comput Biol. 1997 Fall;4(3):311-23
references: 9278062
references: Am J Hum Genet. 2014 Mar 6;94(3):470-8
references: 24607389
references: Nat Genet. 2009 May;41(5):535-43
references: 19377476
references: Nat Genet. 2010 Nov;42(11):969-72
references: 20890277
references: Brain. 2013 Jun;136(Pt 6):1708-17
references: 23687123
references: Nat Methods. 2010 Aug;7(8):575-6
references: 20676075
references: Hum Genet. 2013 Oct;132(10):1177-85
references: 23783460
references: Hum Mol Genet. 2013 Aug 15;22(16):3306-14
references: 23615299
references: Hum Mutat. 2015 Jan;36(1):106-17
references: 25385192
references: Proc Natl Acad Sci U S A. 1996 Nov 12;93(23):13362-6
references: 8917596
references: Trends Genet. 2004 Mar;20(3):146-54
references: 15036808
references: Nat Methods. 2010 Apr;7(4):248-9
references: 20354512
references: Nat Struct Mol Biol. 2006 Dec;13(12):1115-9
references: 17115052
references: Bioinformatics. 2012 Mar 1;28(5):619-27
references: 22238266
references: Nat Rev Genet. 2005 Jan;6(1):46-57
references: 15630421
references: Am J Hum Genet. 2013 Sep 5;93(3):506-14
references: 24011988
references: Eur J Pediatr. 2014 Jul;173(7):967-9
references: 24863632
references: Epilepsia. 2013 Jul;54(7):1270-81
references: 23647072
references: Psychiatr Genet. 2014 Feb;24(1):42-3
references: 24362370
references: Science. 2010 Oct 29;330(6004):635-41
references: 20929736
references: Am J Hum Genet. 2010 Aug 13;87(2):173-88
references: 20655035
references: Nature. 2002 Mar 7;416(6876):99-103
references: 11882901
references: Am J Hum Genet. 2013 Mar 7;92(3):401-6
references: 23395478
references: Nat Struct Mol Biol. 2011 Oct 16;18(11):1227-34
references: 22002225
references: Cell. 2008 Apr 18;133(2):303-13
references: 18423201
references: Am J Hum Genet. 2007 Mar;80(3):393-406
references: 17273961
references: Nat Protoc. 2012 Sep;7(9):1741-54
references: 22936216
references: Nat Genet. 1999 Aug;22(4):394-9
references: 10431247
references: Am J Med Genet. 1991 Sep 15;40(4):406-13
references: 1746601
references: Nat Genet. 2003 May;34(1):27-9
references: 12669065
references: Hum Mutat. 2007 Feb;28(2):207-8
references: 17221867
references: Am J Hum Genet. 2008 Feb;82(2):432-43
references: 18252223
references: Mol Cell Proteomics. 2012 Nov;11(11):1263-73
references: 22872859
references: Am J Hum Genet. 2008 Apr;82(4):1003-10
references: 18342287
references: Neuron. 2001 Jan;29(1):185-96
references: 11182090
references: Eur J Hum Genet. 2014 Jun;22(6):776-83
references: 24169519
references: J Bone Miner Res. 2003 Oct;18(10):1740-7
references: 14584882
references: Am J Hum Genet. 2010 Feb 12;86(2):185-95
references: 20159109
references: Mol Cell Biol. 2010 Sep;30(18):4404-14
references: 20647540
references: Development. 2010 Jul;137(14 ):2365-74
references: 20534669
references: J Cell Sci. 2002 Sep 1;115(Pt 17):3479-90
references: 12154078
references: Nat Genet. 2008 Jun;40(6):776-81
references: 18469813
references: Neuron. 2012 Apr 26;74(2):285-99
references: 22542183
references: Nature. 2011 Sep 21;478(7367):57-63
references: 21937992
references: Mol Cell. 2004 Feb 27;13(4):587-97
references: 14992727
references: Am J Ment Defic. 1972 May;76(6):611-9
references: 5031080
references: EMBO J. 2005 Mar 9;24(5):1079-91
references: 15706348
references: J Appl Genet. 2011 Nov;52(4):437-41
references: 21584729
references: Nat Genet. 2014 Mar;46(3):310-5
references: 24487276
references: Pediatr Neurol. 2013 Dec;49(6):411-416.e1
references: 24084144
references: Neuron. 2001 Jan;29(1):99-113
references: 11182084
references: Neurology. 2014 Apr 15;82(15):1322-30
references: 24647030
references: Am J Hum Genet. 2012 Jan 13;90(1):119-24
references: 22197486
references: J Clin Invest. 2013 May;123(5):2244-56
references: 23563313
references: Genome Res. 2010 Jan;20(1):110-21
references: 19858363
references: Nature. 2012 Sep 6;489(7414):52-5
references: 22955614
references: Nat Protoc. 2009;4(7):1073-81
references: 19561590
references: J Neurosci. 2010 Jan 13;30(2):670-84
references: 20071532
references: J Biol Chem. 1999 Jan 8;274(2):896-902
references: 9873029
references: Mol Cell. 2013 Jun 27;50(6):831-43
references: 23685073
references: Nat Genet. 2010 Jun;42(6):486-8
references: 20473311
references: Am J Med Genet A. 2014 Aug;164A(8):1991-7
references: 24817631
references: J Neurosci. 2008 Dec 31;28(53):14546-56
references: 19118189
references: Mol Biol Cell. 2012 Feb;23(4):716-28
references: 22190735
references: Proc Natl Acad Sci U S A. 2006 Sep 12;103(37):13854-9
references: 16950870
references: Am J Hum Genet. 2013 Aug 8;93(2):249-63
references: 23849776
references: Am J Hum Genet. 2013 Aug 8;93(2):368-83
references: 23871722
references: Neurobiol Dis. 2010 Jul;39(1):3-12
references: 20304068
references: Birth Defects Orig Artic Ser. 1974;10(1):1-100
references: 4458821
references: Am J Med Genet. 1996 Jul 12;64(1):97-106
references: 8826458
references: Am J Med Genet. 1997 Dec 31;73(4):474-9
references: 9415477
references: Neuron. 2013 Jan 23;77(2):235-42
references: 23352160
references: Nature. 2012 Apr 04;485(7397):242-5
references: 22495311
references: Mol Syndromol. 2012 Jan;2(2):60-63
references: 22511892
references: J Biol Chem. 1997 Aug 1;272(31):19099-102
references: 9235896
references: Hugo J. 2009 Dec;3(1-4):41-9
references: 21836662
references: Hum Mutat. 2014 Dec;35(12):1427-35
references: 25219469
references: Mol Psychiatry. 2011 Aug;16(8):867-80
references: 20479760
references: J Med Genet. 2012 May;49(5):332-40
references: 22581972
references: Am J Hum Genet. 2013 May 2;92(5):681-95
references: 23623388
references: J Biol Chem. 2002 Aug 30;277(35):31988-93
references: 12084709
references: Nat Protoc. 2006;1(5):2406-15
references: 17406484
references: J Biol Chem. 2012 Dec 21;287(52):43378-89
references: 23135275
references: Curr Biol. 2014 Mar 31;24(7):786-92
references: 24656827
references: Am J Med Genet A. 2011 Dec;155A(12):3067-70
references: 22002931
references: Genes Dev. 2010 Sep 15;24(18):2043-53
references: 20844015