Research ArticleClinical ResearchDevelopmentGenetics Open Access | 10.1172/JCI199698

Michelle Hua,1 Mohamad-Reza Aghanoori,2 Melissa J. MacPherson,3 Yi Ren,4 Shehani V. Siripala,5 Yifan Yang,2 Yvonne Yan Yan Or,2 Malea Nguyen,4 Robert Duba-Kiss,2,6,7 Daniel Feng,4,7 Laura Williams,2 Christopher J. Gafuik,6,8 GengYi Wang,9 Chloe Quelin,10 Boris Keren,11,12 Sarah Schuhmann,13 Georgia Vasileiou,13,14 Alexia Bourgois,15 Antonio Vitobello,16 Christophe Philippe,17 Zornitza Stark,18,19 Richard J. Leventer,18,19 George McGillivray,18 Frederic Tran Mau-Them,16 Marine Tessarech,20,21 Clément Prouteau,22 Phillis Lakeman,23,24 Mahdi M. Motazacker,23 Donald R. Latner,25 Raymond C. Caylor,26 Yvette van Ierland,27 Eloise Prijoles,26 Angie Lichty,26 Evangelos Theodorou,28 David A. Sweetser,28 Edward Steel,29 Jan Cobben,30 Majed J. Dasouki,31 Daniel G. Calame,32,33,34 Bertrand Isidor,35,36 Benjamin Cogné,35,36 Mitchell Kesler,2,6,7 Brooke Rackel,2 Isabel Clark,2 Deborah M. Kurrasch,2,6,7 G. Campbell Teskey,4 James Ellis,37 Guiqiong He,9 Scott D. Ryan,5 Douglas J. Mahoney,1,6,8,38 A. Micheil Innes,2,6 Jonathan R. Epp,4,7 and Guang Yang1,2,6,7,39

1Department of Biochemistry and Molecular Biology and

2Department of Medical Genetics, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.

3Department of Medical Genetics, University of Alberta, Edmonton, Alberta, Canada.

4Department of Cell Biology and Anatomy;

5Department of Clinical Neuroscience, Cumming School of Medicine;

6Alberta Children’s Hospital Research Institute;

7Hotchkiss Brain Institute, Cumming School of Medicine; and

8Annie Charbonneau Cancer Institute, University of Calgary, Calgary, Alberta, Canada.

9Center for Neuroscience Research, School of Basic Medical Sciences, Chongqing Medical University, Chongqing, China.

10Service de Génétique Clinique, Centre de Référence «Anomalies du Développement et Syndromes Malformatifs» de l’Inter-région Ouest, CHU Rennes Hôpital Sud, Rennes, France.

11Department of Genetics, La Pitié-Salpêtrière Hospital, Assistance Publique Hospital of Paris, Paris, France.

12Sorbonne University, Paris, France.

13Institute of Human Genetics, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany.

14Department of Human Genetics, Hannover Medical School, Hannover, Germany.

15Service de Génétique, Centre Hospitalier Universitaire de Caen, Caen, Basse-Normandie, France.

16Université Bourgogne Europe, CHU Dijon Bourgogne, Laboratoire de Génomique Médicale, Centre Neomics, FHU TRANSLAD, Centre de recherche Translationnelle en Médecine moléculaire – INSERM UMR1231, équipe GAD, Dijon, France.

17Laboratoire de Génétique, Hôpital de Mercy, CHR Metz-Thionville, Metz, France.

18Victorian Clinical Genetics Services, Murdoch Children’s Research Institute, Melbourne, Victoria, Australia.

19Department of Paediatrics, University of Melbourne, Melbourne, Victoria, Australia.

20Department of Medical Genetics, Angers University Hospital, Angers, France.

21Mitovasc Unit, UMR CNRS 6015 INSERM 1083, University of Angers, Angers, France.

22Service de Génétique Médicale, CHU d’Angers, Angers, France.

23Amsterdam UMC, Department of Human Genetics, University of Amsterdam, Amsterdam, Netherlands.

24Amsterdam Reproduction & Development Research Institute, Amsterdam, Netherlands.

25HudsonAlpha Institute for Biotechnology, Huntsville, Alabama, USA.

26Greenwood Genetic Center, Greenwood, South Carolina, USA.

27Department of Clinical Genetics, Erasmus University Medical Center, Rotterdam, Netherlands.

28Center for Genomic Medicine, Divisions of Pediatric Hematology/Oncology and Medical Genetics and Metabolism, Department of Pediatrics, Massachusetts General Hospital, Boston, Massachusetts, USA.

29Clinical Genetics, Great Ormond Street Hospital, London, United Kingdom.

30Section of Genomics and Genetics, Imperial College London, London, United Kingdom.

31AdventHealth Genomics & Personalized Health at Orlando, Department of Medical Genetics & Genomics, Orlando, Florida, USA.

32Section of Pediatric Neurology and Developmental Neurosciences, Department of Pediatrics, and

33Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas, USA.

34Jan and Dan Duncan Neurological Research Institute, Texas Children’s Hospital, Houston, Texas, USA.

35Nantes Université, CHU de Nantes, CNRS, INSERM, l’institut du thorax, Nantes, France.

36Nantes Université, CHU de Nantes, Service de Génétique médicale, Nantes, France.

37Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada.

38Department of Microbiology, Immunology and Infectious Diseases, Snyder Institute for Chronic Diseases, and

39Owerko Center, University of Calgary, Calgary, Alberta, Canada.

Address correspondence to: Guang Yang or Jonathan R. Epp, 3330 Hospital Dr. NW, Calgary, Alberta, T2N 4N1, Canada. Phone: 403.220.6203; Email: guang.yang2@ucalgary.ca (GY); Phone: 403.210.6349; Email: jonathan.epp1@ucalgary.ca (JRE). Or to: A. Micheil Innes, 28 Oki Dr., Calgary, Alberta, T3B 6A8, Canada. Phone: 403.955.7588; Email: micheil.innes@albertahealthservices.ca.

Authorship note: MH, MRA, and MJM contributed equally to this work as co–first authors.

Find articles by Hua, M. in: PubMed | Google Scholar

1Department of Biochemistry and Molecular Biology and

2Department of Medical Genetics, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.

3Department of Medical Genetics, University of Alberta, Edmonton, Alberta, Canada.

4Department of Cell Biology and Anatomy;

5Department of Clinical Neuroscience, Cumming School of Medicine;

6Alberta Children’s Hospital Research Institute;

7Hotchkiss Brain Institute, Cumming School of Medicine; and

8Annie Charbonneau Cancer Institute, University of Calgary, Calgary, Alberta, Canada.

9Center for Neuroscience Research, School of Basic Medical Sciences, Chongqing Medical University, Chongqing, China.

10Service de Génétique Clinique, Centre de Référence «Anomalies du Développement et Syndromes Malformatifs» de l’Inter-région Ouest, CHU Rennes Hôpital Sud, Rennes, France.

11Department of Genetics, La Pitié-Salpêtrière Hospital, Assistance Publique Hospital of Paris, Paris, France.

12Sorbonne University, Paris, France.

13Institute of Human Genetics, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany.

14Department of Human Genetics, Hannover Medical School, Hannover, Germany.

15Service de Génétique, Centre Hospitalier Universitaire de Caen, Caen, Basse-Normandie, France.

16Université Bourgogne Europe, CHU Dijon Bourgogne, Laboratoire de Génomique Médicale, Centre Neomics, FHU TRANSLAD, Centre de recherche Translationnelle en Médecine moléculaire – INSERM UMR1231, équipe GAD, Dijon, France.

17Laboratoire de Génétique, Hôpital de Mercy, CHR Metz-Thionville, Metz, France.

18Victorian Clinical Genetics Services, Murdoch Children’s Research Institute, Melbourne, Victoria, Australia.

19Department of Paediatrics, University of Melbourne, Melbourne, Victoria, Australia.

20Department of Medical Genetics, Angers University Hospital, Angers, France.

21Mitovasc Unit, UMR CNRS 6015 INSERM 1083, University of Angers, Angers, France.

22Service de Génétique Médicale, CHU d’Angers, Angers, France.

23Amsterdam UMC, Department of Human Genetics, University of Amsterdam, Amsterdam, Netherlands.

24Amsterdam Reproduction & Development Research Institute, Amsterdam, Netherlands.

25HudsonAlpha Institute for Biotechnology, Huntsville, Alabama, USA.

26Greenwood Genetic Center, Greenwood, South Carolina, USA.

27Department of Clinical Genetics, Erasmus University Medical Center, Rotterdam, Netherlands.

28Center for Genomic Medicine, Divisions of Pediatric Hematology/Oncology and Medical Genetics and Metabolism, Department of Pediatrics, Massachusetts General Hospital, Boston, Massachusetts, USA.

29Clinical Genetics, Great Ormond Street Hospital, London, United Kingdom.

30Section of Genomics and Genetics, Imperial College London, London, United Kingdom.

31AdventHealth Genomics & Personalized Health at Orlando, Department of Medical Genetics & Genomics, Orlando, Florida, USA.

32Section of Pediatric Neurology and Developmental Neurosciences, Department of Pediatrics, and

33Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas, USA.

34Jan and Dan Duncan Neurological Research Institute, Texas Children’s Hospital, Houston, Texas, USA.

35Nantes Université, CHU de Nantes, CNRS, INSERM, l’institut du thorax, Nantes, France.

36Nantes Université, CHU de Nantes, Service de Génétique médicale, Nantes, France.

37Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada.

38Department of Microbiology, Immunology and Infectious Diseases, Snyder Institute for Chronic Diseases, and

39Owerko Center, University of Calgary, Calgary, Alberta, Canada.

Address correspondence to: Guang Yang or Jonathan R. Epp, 3330 Hospital Dr. NW, Calgary, Alberta, T2N 4N1, Canada. Phone: 403.220.6203; Email: guang.yang2@ucalgary.ca (GY); Phone: 403.210.6349; Email: jonathan.epp1@ucalgary.ca (JRE). Or to: A. Micheil Innes, 28 Oki Dr., Calgary, Alberta, T3B 6A8, Canada. Phone: 403.955.7588; Email: micheil.innes@albertahealthservices.ca.

Authorship note: MH, MRA, and MJM contributed equally to this work as co–first authors.

Find articles by Aghanoori, M. in: PubMed | Google Scholar

1Department of Biochemistry and Molecular Biology and

2Department of Medical Genetics, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.

3Department of Medical Genetics, University of Alberta, Edmonton, Alberta, Canada.

4Department of Cell Biology and Anatomy;

5Department of Clinical Neuroscience, Cumming School of Medicine;

6Alberta Children’s Hospital Research Institute;

7Hotchkiss Brain Institute, Cumming School of Medicine; and

8Annie Charbonneau Cancer Institute, University of Calgary, Calgary, Alberta, Canada.

9Center for Neuroscience Research, School of Basic Medical Sciences, Chongqing Medical University, Chongqing, China.

10Service de Génétique Clinique, Centre de Référence «Anomalies du Développement et Syndromes Malformatifs» de l’Inter-région Ouest, CHU Rennes Hôpital Sud, Rennes, France.

11Department of Genetics, La Pitié-Salpêtrière Hospital, Assistance Publique Hospital of Paris, Paris, France.

12Sorbonne University, Paris, France.

13Institute of Human Genetics, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany.

14Department of Human Genetics, Hannover Medical School, Hannover, Germany.

15Service de Génétique, Centre Hospitalier Universitaire de Caen, Caen, Basse-Normandie, France.

16Université Bourgogne Europe, CHU Dijon Bourgogne, Laboratoire de Génomique Médicale, Centre Neomics, FHU TRANSLAD, Centre de recherche Translationnelle en Médecine moléculaire – INSERM UMR1231, équipe GAD, Dijon, France.

17Laboratoire de Génétique, Hôpital de Mercy, CHR Metz-Thionville, Metz, France.

18Victorian Clinical Genetics Services, Murdoch Children’s Research Institute, Melbourne, Victoria, Australia.

19Department of Paediatrics, University of Melbourne, Melbourne, Victoria, Australia.

20Department of Medical Genetics, Angers University Hospital, Angers, France.

21Mitovasc Unit, UMR CNRS 6015 INSERM 1083, University of Angers, Angers, France.

22Service de Génétique Médicale, CHU d’Angers, Angers, France.

23Amsterdam UMC, Department of Human Genetics, University of Amsterdam, Amsterdam, Netherlands.

24Amsterdam Reproduction & Development Research Institute, Amsterdam, Netherlands.

25HudsonAlpha Institute for Biotechnology, Huntsville, Alabama, USA.

26Greenwood Genetic Center, Greenwood, South Carolina, USA.

27Department of Clinical Genetics, Erasmus University Medical Center, Rotterdam, Netherlands.

28Center for Genomic Medicine, Divisions of Pediatric Hematology/Oncology and Medical Genetics and Metabolism, Department of Pediatrics, Massachusetts General Hospital, Boston, Massachusetts, USA.

29Clinical Genetics, Great Ormond Street Hospital, London, United Kingdom.

30Section of Genomics and Genetics, Imperial College London, London, United Kingdom.

31AdventHealth Genomics & Personalized Health at Orlando, Department of Medical Genetics & Genomics, Orlando, Florida, USA.

32Section of Pediatric Neurology and Developmental Neurosciences, Department of Pediatrics, and

33Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas, USA.

34Jan and Dan Duncan Neurological Research Institute, Texas Children’s Hospital, Houston, Texas, USA.

35Nantes Université, CHU de Nantes, CNRS, INSERM, l’institut du thorax, Nantes, France.

36Nantes Université, CHU de Nantes, Service de Génétique médicale, Nantes, France.

37Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada.

38Department of Microbiology, Immunology and Infectious Diseases, Snyder Institute for Chronic Diseases, and

39Owerko Center, University of Calgary, Calgary, Alberta, Canada.

Address correspondence to: Guang Yang or Jonathan R. Epp, 3330 Hospital Dr. NW, Calgary, Alberta, T2N 4N1, Canada. Phone: 403.220.6203; Email: guang.yang2@ucalgary.ca (GY); Phone: 403.210.6349; Email: jonathan.epp1@ucalgary.ca (JRE). Or to: A. Micheil Innes, 28 Oki Dr., Calgary, Alberta, T3B 6A8, Canada. Phone: 403.955.7588; Email: micheil.innes@albertahealthservices.ca.

Authorship note: MH, MRA, and MJM contributed equally to this work as co–first authors.

Find articles by MacPherson, M. in: PubMed | Google Scholar

1Department of Biochemistry and Molecular Biology and

2Department of Medical Genetics, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.

3Department of Medical Genetics, University of Alberta, Edmonton, Alberta, Canada.

4Department of Cell Biology and Anatomy;

5Department of Clinical Neuroscience, Cumming School of Medicine;

6Alberta Children’s Hospital Research Institute;

7Hotchkiss Brain Institute, Cumming School of Medicine; and

8Annie Charbonneau Cancer Institute, University of Calgary, Calgary, Alberta, Canada.

9Center for Neuroscience Research, School of Basic Medical Sciences, Chongqing Medical University, Chongqing, China.

10Service de Génétique Clinique, Centre de Référence «Anomalies du Développement et Syndromes Malformatifs» de l’Inter-région Ouest, CHU Rennes Hôpital Sud, Rennes, France.

11Department of Genetics, La Pitié-Salpêtrière Hospital, Assistance Publique Hospital of Paris, Paris, France.

12Sorbonne University, Paris, France.

13Institute of Human Genetics, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany.

14Department of Human Genetics, Hannover Medical School, Hannover, Germany.

15Service de Génétique, Centre Hospitalier Universitaire de Caen, Caen, Basse-Normandie, France.

16Université Bourgogne Europe, CHU Dijon Bourgogne, Laboratoire de Génomique Médicale, Centre Neomics, FHU TRANSLAD, Centre de recherche Translationnelle en Médecine moléculaire – INSERM UMR1231, équipe GAD, Dijon, France.

17Laboratoire de Génétique, Hôpital de Mercy, CHR Metz-Thionville, Metz, France.

18Victorian Clinical Genetics Services, Murdoch Children’s Research Institute, Melbourne, Victoria, Australia.

19Department of Paediatrics, University of Melbourne, Melbourne, Victoria, Australia.

20Department of Medical Genetics, Angers University Hospital, Angers, France.

21Mitovasc Unit, UMR CNRS 6015 INSERM 1083, University of Angers, Angers, France.

22Service de Génétique Médicale, CHU d’Angers, Angers, France.

23Amsterdam UMC, Department of Human Genetics, University of Amsterdam, Amsterdam, Netherlands.

24Amsterdam Reproduction & Development Research Institute, Amsterdam, Netherlands.

25HudsonAlpha Institute for Biotechnology, Huntsville, Alabama, USA.

26Greenwood Genetic Center, Greenwood, South Carolina, USA.

27Department of Clinical Genetics, Erasmus University Medical Center, Rotterdam, Netherlands.

28Center for Genomic Medicine, Divisions of Pediatric Hematology/Oncology and Medical Genetics and Metabolism, Department of Pediatrics, Massachusetts General Hospital, Boston, Massachusetts, USA.

29Clinical Genetics, Great Ormond Street Hospital, London, United Kingdom.

30Section of Genomics and Genetics, Imperial College London, London, United Kingdom.

31AdventHealth Genomics & Personalized Health at Orlando, Department of Medical Genetics & Genomics, Orlando, Florida, USA.

32Section of Pediatric Neurology and Developmental Neurosciences, Department of Pediatrics, and

33Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas, USA.

34Jan and Dan Duncan Neurological Research Institute, Texas Children’s Hospital, Houston, Texas, USA.

35Nantes Université, CHU de Nantes, CNRS, INSERM, l’institut du thorax, Nantes, France.

36Nantes Université, CHU de Nantes, Service de Génétique médicale, Nantes, France.

37Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada.

38Department of Microbiology, Immunology and Infectious Diseases, Snyder Institute for Chronic Diseases, and

39Owerko Center, University of Calgary, Calgary, Alberta, Canada.

Address correspondence to: Guang Yang or Jonathan R. Epp, 3330 Hospital Dr. NW, Calgary, Alberta, T2N 4N1, Canada. Phone: 403.220.6203; Email: guang.yang2@ucalgary.ca (GY); Phone: 403.210.6349; Email: jonathan.epp1@ucalgary.ca (JRE). Or to: A. Micheil Innes, 28 Oki Dr., Calgary, Alberta, T3B 6A8, Canada. Phone: 403.955.7588; Email: micheil.innes@albertahealthservices.ca.

Authorship note: MH, MRA, and MJM contributed equally to this work as co–first authors.

Find articles by Ren, Y. in: PubMed | Google Scholar

1Department of Biochemistry and Molecular Biology and

2Department of Medical Genetics, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.

3Department of Medical Genetics, University of Alberta, Edmonton, Alberta, Canada.

4Department of Cell Biology and Anatomy;

5Department of Clinical Neuroscience, Cumming School of Medicine;

6Alberta Children’s Hospital Research Institute;

7Hotchkiss Brain Institute, Cumming School of Medicine; and

8Annie Charbonneau Cancer Institute, University of Calgary, Calgary, Alberta, Canada.

9Center for Neuroscience Research, School of Basic Medical Sciences, Chongqing Medical University, Chongqing, China.

10Service de Génétique Clinique, Centre de Référence «Anomalies du Développement et Syndromes Malformatifs» de l’Inter-région Ouest, CHU Rennes Hôpital Sud, Rennes, France.

11Department of Genetics, La Pitié-Salpêtrière Hospital, Assistance Publique Hospital of Paris, Paris, France.

12Sorbonne University, Paris, France.

13Institute of Human Genetics, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany.

14Department of Human Genetics, Hannover Medical School, Hannover, Germany.

15Service de Génétique, Centre Hospitalier Universitaire de Caen, Caen, Basse-Normandie, France.

16Université Bourgogne Europe, CHU Dijon Bourgogne, Laboratoire de Génomique Médicale, Centre Neomics, FHU TRANSLAD, Centre de recherche Translationnelle en Médecine moléculaire – INSERM UMR1231, équipe GAD, Dijon, France.

17Laboratoire de Génétique, Hôpital de Mercy, CHR Metz-Thionville, Metz, France.

18Victorian Clinical Genetics Services, Murdoch Children’s Research Institute, Melbourne, Victoria, Australia.

19Department of Paediatrics, University of Melbourne, Melbourne, Victoria, Australia.

20Department of Medical Genetics, Angers University Hospital, Angers, France.

21Mitovasc Unit, UMR CNRS 6015 INSERM 1083, University of Angers, Angers, France.

22Service de Génétique Médicale, CHU d’Angers, Angers, France.

23Amsterdam UMC, Department of Human Genetics, University of Amsterdam, Amsterdam, Netherlands.

24Amsterdam Reproduction & Development Research Institute, Amsterdam, Netherlands.

25HudsonAlpha Institute for Biotechnology, Huntsville, Alabama, USA.

26Greenwood Genetic Center, Greenwood, South Carolina, USA.

27Department of Clinical Genetics, Erasmus University Medical Center, Rotterdam, Netherlands.

28Center for Genomic Medicine, Divisions of Pediatric Hematology/Oncology and Medical Genetics and Metabolism, Department of Pediatrics, Massachusetts General Hospital, Boston, Massachusetts, USA.

29Clinical Genetics, Great Ormond Street Hospital, London, United Kingdom.

30Section of Genomics and Genetics, Imperial College London, London, United Kingdom.

31AdventHealth Genomics & Personalized Health at Orlando, Department of Medical Genetics & Genomics, Orlando, Florida, USA.

32Section of Pediatric Neurology and Developmental Neurosciences, Department of Pediatrics, and

33Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas, USA.

34Jan and Dan Duncan Neurological Research Institute, Texas Children’s Hospital, Houston, Texas, USA.

35Nantes Université, CHU de Nantes, CNRS, INSERM, l’institut du thorax, Nantes, France.

36Nantes Université, CHU de Nantes, Service de Génétique médicale, Nantes, France.

37Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada.

38Department of Microbiology, Immunology and Infectious Diseases, Snyder Institute for Chronic Diseases, and

39Owerko Center, University of Calgary, Calgary, Alberta, Canada.

Address correspondence to: Guang Yang or Jonathan R. Epp, 3330 Hospital Dr. NW, Calgary, Alberta, T2N 4N1, Canada. Phone: 403.220.6203; Email: guang.yang2@ucalgary.ca (GY); Phone: 403.210.6349; Email: jonathan.epp1@ucalgary.ca (JRE). Or to: A. Micheil Innes, 28 Oki Dr., Calgary, Alberta, T3B 6A8, Canada. Phone: 403.955.7588; Email: micheil.innes@albertahealthservices.ca.

Authorship note: MH, MRA, and MJM contributed equally to this work as co–first authors.

Find articles by Siripala, S. in: PubMed | Google Scholar

1Department of Biochemistry and Molecular Biology and

2Department of Medical Genetics, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.

3Department of Medical Genetics, University of Alberta, Edmonton, Alberta, Canada.

4Department of Cell Biology and Anatomy;

5Department of Clinical Neuroscience, Cumming School of Medicine;

6Alberta Children’s Hospital Research Institute;

7Hotchkiss Brain Institute, Cumming School of Medicine; and

8Annie Charbonneau Cancer Institute, University of Calgary, Calgary, Alberta, Canada.

9Center for Neuroscience Research, School of Basic Medical Sciences, Chongqing Medical University, Chongqing, China.

10Service de Génétique Clinique, Centre de Référence «Anomalies du Développement et Syndromes Malformatifs» de l’Inter-région Ouest, CHU Rennes Hôpital Sud, Rennes, France.

11Department of Genetics, La Pitié-Salpêtrière Hospital, Assistance Publique Hospital of Paris, Paris, France.

12Sorbonne University, Paris, France.

13Institute of Human Genetics, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany.

14Department of Human Genetics, Hannover Medical School, Hannover, Germany.

15Service de Génétique, Centre Hospitalier Universitaire de Caen, Caen, Basse-Normandie, France.

16Université Bourgogne Europe, CHU Dijon Bourgogne, Laboratoire de Génomique Médicale, Centre Neomics, FHU TRANSLAD, Centre de recherche Translationnelle en Médecine moléculaire – INSERM UMR1231, équipe GAD, Dijon, France.

17Laboratoire de Génétique, Hôpital de Mercy, CHR Metz-Thionville, Metz, France.

18Victorian Clinical Genetics Services, Murdoch Children’s Research Institute, Melbourne, Victoria, Australia.

19Department of Paediatrics, University of Melbourne, Melbourne, Victoria, Australia.

20Department of Medical Genetics, Angers University Hospital, Angers, France.

21Mitovasc Unit, UMR CNRS 6015 INSERM 1083, University of Angers, Angers, France.

22Service de Génétique Médicale, CHU d’Angers, Angers, France.

23Amsterdam UMC, Department of Human Genetics, University of Amsterdam, Amsterdam, Netherlands.

24Amsterdam Reproduction & Development Research Institute, Amsterdam, Netherlands.

25HudsonAlpha Institute for Biotechnology, Huntsville, Alabama, USA.

26Greenwood Genetic Center, Greenwood, South Carolina, USA.

27Department of Clinical Genetics, Erasmus University Medical Center, Rotterdam, Netherlands.

28Center for Genomic Medicine, Divisions of Pediatric Hematology/Oncology and Medical Genetics and Metabolism, Department of Pediatrics, Massachusetts General Hospital, Boston, Massachusetts, USA.

29Clinical Genetics, Great Ormond Street Hospital, London, United Kingdom.

30Section of Genomics and Genetics, Imperial College London, London, United Kingdom.

31AdventHealth Genomics & Personalized Health at Orlando, Department of Medical Genetics & Genomics, Orlando, Florida, USA.

32Section of Pediatric Neurology and Developmental Neurosciences, Department of Pediatrics, and

33Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas, USA.

34Jan and Dan Duncan Neurological Research Institute, Texas Children’s Hospital, Houston, Texas, USA.

35Nantes Université, CHU de Nantes, CNRS, INSERM, l’institut du thorax, Nantes, France.

36Nantes Université, CHU de Nantes, Service de Génétique médicale, Nantes, France.

37Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada.

38Department of Microbiology, Immunology and Infectious Diseases, Snyder Institute for Chronic Diseases, and

39Owerko Center, University of Calgary, Calgary, Alberta, Canada.

Address correspondence to: Guang Yang or Jonathan R. Epp, 3330 Hospital Dr. NW, Calgary, Alberta, T2N 4N1, Canada. Phone: 403.220.6203; Email: guang.yang2@ucalgary.ca (GY); Phone: 403.210.6349; Email: jonathan.epp1@ucalgary.ca (JRE). Or to: A. Micheil Innes, 28 Oki Dr., Calgary, Alberta, T3B 6A8, Canada. Phone: 403.955.7588; Email: micheil.innes@albertahealthservices.ca.

Authorship note: MH, MRA, and MJM contributed equally to this work as co–first authors.

Find articles by Yang, Y. in: PubMed | Google Scholar

1Department of Biochemistry and Molecular Biology and

2Department of Medical Genetics, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.

3Department of Medical Genetics, University of Alberta, Edmonton, Alberta, Canada.

4Department of Cell Biology and Anatomy;

5Department of Clinical Neuroscience, Cumming School of Medicine;

6Alberta Children’s Hospital Research Institute;

7Hotchkiss Brain Institute, Cumming School of Medicine; and

8Annie Charbonneau Cancer Institute, University of Calgary, Calgary, Alberta, Canada.

9Center for Neuroscience Research, School of Basic Medical Sciences, Chongqing Medical University, Chongqing, China.

10Service de Génétique Clinique, Centre de Référence «Anomalies du Développement et Syndromes Malformatifs» de l’Inter-région Ouest, CHU Rennes Hôpital Sud, Rennes, France.

11Department of Genetics, La Pitié-Salpêtrière Hospital, Assistance Publique Hospital of Paris, Paris, France.

12Sorbonne University, Paris, France.

13Institute of Human Genetics, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany.

14Department of Human Genetics, Hannover Medical School, Hannover, Germany.

15Service de Génétique, Centre Hospitalier Universitaire de Caen, Caen, Basse-Normandie, France.

16Université Bourgogne Europe, CHU Dijon Bourgogne, Laboratoire de Génomique Médicale, Centre Neomics, FHU TRANSLAD, Centre de recherche Translationnelle en Médecine moléculaire – INSERM UMR1231, équipe GAD, Dijon, France.

17Laboratoire de Génétique, Hôpital de Mercy, CHR Metz-Thionville, Metz, France.

18Victorian Clinical Genetics Services, Murdoch Children’s Research Institute, Melbourne, Victoria, Australia.

19Department of Paediatrics, University of Melbourne, Melbourne, Victoria, Australia.

20Department of Medical Genetics, Angers University Hospital, Angers, France.

21Mitovasc Unit, UMR CNRS 6015 INSERM 1083, University of Angers, Angers, France.

22Service de Génétique Médicale, CHU d’Angers, Angers, France.

23Amsterdam UMC, Department of Human Genetics, University of Amsterdam, Amsterdam, Netherlands.

24Amsterdam Reproduction & Development Research Institute, Amsterdam, Netherlands.

25HudsonAlpha Institute for Biotechnology, Huntsville, Alabama, USA.

26Greenwood Genetic Center, Greenwood, South Carolina, USA.

27Department of Clinical Genetics, Erasmus University Medical Center, Rotterdam, Netherlands.

28Center for Genomic Medicine, Divisions of Pediatric Hematology/Oncology and Medical Genetics and Metabolism, Department of Pediatrics, Massachusetts General Hospital, Boston, Massachusetts, USA.

29Clinical Genetics, Great Ormond Street Hospital, London, United Kingdom.

30Section of Genomics and Genetics, Imperial College London, London, United Kingdom.

31AdventHealth Genomics & Personalized Health at Orlando, Department of Medical Genetics & Genomics, Orlando, Florida, USA.

32Section of Pediatric Neurology and Developmental Neurosciences, Department of Pediatrics, and

33Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas, USA.

34Jan and Dan Duncan Neurological Research Institute, Texas Children’s Hospital, Houston, Texas, USA.

35Nantes Université, CHU de Nantes, CNRS, INSERM, l’institut du thorax, Nantes, France.

36Nantes Université, CHU de Nantes, Service de Génétique médicale, Nantes, France.

37Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada.

38Department of Microbiology, Immunology and Infectious Diseases, Snyder Institute for Chronic Diseases, and

39Owerko Center, University of Calgary, Calgary, Alberta, Canada.

Address correspondence to: Guang Yang or Jonathan R. Epp, 3330 Hospital Dr. NW, Calgary, Alberta, T2N 4N1, Canada. Phone: 403.220.6203; Email: guang.yang2@ucalgary.ca (GY); Phone: 403.210.6349; Email: jonathan.epp1@ucalgary.ca (JRE). Or to: A. Micheil Innes, 28 Oki Dr., Calgary, Alberta, T3B 6A8, Canada. Phone: 403.955.7588; Email: micheil.innes@albertahealthservices.ca.

Authorship note: MH, MRA, and MJM contributed equally to this work as co–first authors.

Find articles by Or, Y. in: PubMed | Google Scholar

1Department of Biochemistry and Molecular Biology and

2Department of Medical Genetics, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.

3Department of Medical Genetics, University of Alberta, Edmonton, Alberta, Canada.

4Department of Cell Biology and Anatomy;

5Department of Clinical Neuroscience, Cumming School of Medicine;

6Alberta Children’s Hospital Research Institute;

7Hotchkiss Brain Institute, Cumming School of Medicine; and

8Annie Charbonneau Cancer Institute, University of Calgary, Calgary, Alberta, Canada.

9Center for Neuroscience Research, School of Basic Medical Sciences, Chongqing Medical University, Chongqing, China.

10Service de Génétique Clinique, Centre de Référence «Anomalies du Développement et Syndromes Malformatifs» de l’Inter-région Ouest, CHU Rennes Hôpital Sud, Rennes, France.

11Department of Genetics, La Pitié-Salpêtrière Hospital, Assistance Publique Hospital of Paris, Paris, France.

12Sorbonne University, Paris, France.

13Institute of Human Genetics, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany.

14Department of Human Genetics, Hannover Medical School, Hannover, Germany.

15Service de Génétique, Centre Hospitalier Universitaire de Caen, Caen, Basse-Normandie, France.

16Université Bourgogne Europe, CHU Dijon Bourgogne, Laboratoire de Génomique Médicale, Centre Neomics, FHU TRANSLAD, Centre de recherche Translationnelle en Médecine moléculaire – INSERM UMR1231, équipe GAD, Dijon, France.

17Laboratoire de Génétique, Hôpital de Mercy, CHR Metz-Thionville, Metz, France.

18Victorian Clinical Genetics Services, Murdoch Children’s Research Institute, Melbourne, Victoria, Australia.

19Department of Paediatrics, University of Melbourne, Melbourne, Victoria, Australia.

20Department of Medical Genetics, Angers University Hospital, Angers, France.

21Mitovasc Unit, UMR CNRS 6015 INSERM 1083, University of Angers, Angers, France.

22Service de Génétique Médicale, CHU d’Angers, Angers, France.

23Amsterdam UMC, Department of Human Genetics, University of Amsterdam, Amsterdam, Netherlands.

24Amsterdam Reproduction & Development Research Institute, Amsterdam, Netherlands.

25HudsonAlpha Institute for Biotechnology, Huntsville, Alabama, USA.

26Greenwood Genetic Center, Greenwood, South Carolina, USA.

27Department of Clinical Genetics, Erasmus University Medical Center, Rotterdam, Netherlands.

28Center for Genomic Medicine, Divisions of Pediatric Hematology/Oncology and Medical Genetics and Metabolism, Department of Pediatrics, Massachusetts General Hospital, Boston, Massachusetts, USA.

29Clinical Genetics, Great Ormond Street Hospital, London, United Kingdom.

30Section of Genomics and Genetics, Imperial College London, London, United Kingdom.

31AdventHealth Genomics & Personalized Health at Orlando, Department of Medical Genetics & Genomics, Orlando, Florida, USA.

32Section of Pediatric Neurology and Developmental Neurosciences, Department of Pediatrics, and

33Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas, USA.

34Jan and Dan Duncan Neurological Research Institute, Texas Children’s Hospital, Houston, Texas, USA.

35Nantes Université, CHU de Nantes, CNRS, INSERM, l’institut du thorax, Nantes, France.

36Nantes Université, CHU de Nantes, Service de Génétique médicale, Nantes, France.

37Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada.

38Department of Microbiology, Immunology and Infectious Diseases, Snyder Institute for Chronic Diseases, and

39Owerko Center, University of Calgary, Calgary, Alberta, Canada.

Address correspondence to: Guang Yang or Jonathan R. Epp, 3330 Hospital Dr. NW, Calgary, Alberta, T2N 4N1, Canada. Phone: 403.220.6203; Email: guang.yang2@ucalgary.ca (GY); Phone: 403.210.6349; Email: jonathan.epp1@ucalgary.ca (JRE). Or to: A. Micheil Innes, 28 Oki Dr., Calgary, Alberta, T3B 6A8, Canada. Phone: 403.955.7588; Email: micheil.innes@albertahealthservices.ca.

Authorship note: MH, MRA, and MJM contributed equally to this work as co–first authors.

Find articles by Nguyen, M. in: PubMed | Google Scholar

1Department of Biochemistry and Molecular Biology and

2Department of Medical Genetics, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.

3Department of Medical Genetics, University of Alberta, Edmonton, Alberta, Canada.

4Department of Cell Biology and Anatomy;

5Department of Clinical Neuroscience, Cumming School of Medicine;

6Alberta Children’s Hospital Research Institute;

7Hotchkiss Brain Institute, Cumming School of Medicine; and

8Annie Charbonneau Cancer Institute, University of Calgary, Calgary, Alberta, Canada.

9Center for Neuroscience Research, School of Basic Medical Sciences, Chongqing Medical University, Chongqing, China.

10Service de Génétique Clinique, Centre de Référence «Anomalies du Développement et Syndromes Malformatifs» de l’Inter-région Ouest, CHU Rennes Hôpital Sud, Rennes, France.

11Department of Genetics, La Pitié-Salpêtrière Hospital, Assistance Publique Hospital of Paris, Paris, France.

12Sorbonne University, Paris, France.

13Institute of Human Genetics, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany.

14Department of Human Genetics, Hannover Medical School, Hannover, Germany.

15Service de Génétique, Centre Hospitalier Universitaire de Caen, Caen, Basse-Normandie, France.

16Université Bourgogne Europe, CHU Dijon Bourgogne, Laboratoire de Génomique Médicale, Centre Neomics, FHU TRANSLAD, Centre de recherche Translationnelle en Médecine moléculaire – INSERM UMR1231, équipe GAD, Dijon, France.

17Laboratoire de Génétique, Hôpital de Mercy, CHR Metz-Thionville, Metz, France.

18Victorian Clinical Genetics Services, Murdoch Children’s Research Institute, Melbourne, Victoria, Australia.

19Department of Paediatrics, University of Melbourne, Melbourne, Victoria, Australia.

20Department of Medical Genetics, Angers University Hospital, Angers, France.

21Mitovasc Unit, UMR CNRS 6015 INSERM 1083, University of Angers, Angers, France.

22Service de Génétique Médicale, CHU d’Angers, Angers, France.

23Amsterdam UMC, Department of Human Genetics, University of Amsterdam, Amsterdam, Netherlands.

24Amsterdam Reproduction & Development Research Institute, Amsterdam, Netherlands.

25HudsonAlpha Institute for Biotechnology, Huntsville, Alabama, USA.

26Greenwood Genetic Center, Greenwood, South Carolina, USA.

27Department of Clinical Genetics, Erasmus University Medical Center, Rotterdam, Netherlands.

28Center for Genomic Medicine, Divisions of Pediatric Hematology/Oncology and Medical Genetics and Metabolism, Department of Pediatrics, Massachusetts General Hospital, Boston, Massachusetts, USA.

29Clinical Genetics, Great Ormond Street Hospital, London, United Kingdom.

30Section of Genomics and Genetics, Imperial College London, London, United Kingdom.

31AdventHealth Genomics & Personalized Health at Orlando, Department of Medical Genetics & Genomics, Orlando, Florida, USA.

32Section of Pediatric Neurology and Developmental Neurosciences, Department of Pediatrics, and

33Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas, USA.

34Jan and Dan Duncan Neurological Research Institute, Texas Children’s Hospital, Houston, Texas, USA.

35Nantes Université, CHU de Nantes, CNRS, INSERM, l’institut du thorax, Nantes, France.

36Nantes Université, CHU de Nantes, Service de Génétique médicale, Nantes, France.

37Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada.

38Department of Microbiology, Immunology and Infectious Diseases, Snyder Institute for Chronic Diseases, and

39Owerko Center, University of Calgary, Calgary, Alberta, Canada.

Address correspondence to: Guang Yang or Jonathan R. Epp, 3330 Hospital Dr. NW, Calgary, Alberta, T2N 4N1, Canada. Phone: 403.220.6203; Email: guang.yang2@ucalgary.ca (GY); Phone: 403.210.6349; Email: jonathan.epp1@ucalgary.ca (JRE). Or to: A. Micheil Innes, 28 Oki Dr., Calgary, Alberta, T3B 6A8, Canada. Phone: 403.955.7588; Email: micheil.innes@albertahealthservices.ca.

Authorship note: MH, MRA, and MJM contributed equally to this work as co–first authors.

Find articles by Duba-Kiss, R. in: PubMed | Google Scholar

1Department of Biochemistry and Molecular Biology and

2Department of Medical Genetics, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.

3Department of Medical Genetics, University of Alberta, Edmonton, Alberta, Canada.

4Department of Cell Biology and Anatomy;

5Department of Clinical Neuroscience, Cumming School of Medicine;