Research ArticleGeneticsOncology Open Access | 10.1172/jci.insight.170079

Ghada M. H. Abdel-Salam,1 Susanne Hellmuth,2 Elise Gradhand,3 Stephan Käseberg,4 Jennifer Winter,4 Ann-Sophie Pabst,4 Maha M. Eid,5 Holger Thiele,6 Peter Nürnberg,6,7,8 Birgit S. Budde,6 Mohammad Reza Toliat,6 Ines B. Brecht,9 Christopher Schroeder,10 Axel Gschwind,10 Stephan Ossowski,10 Friederike Häuser,11 Heidi Rossmann,11 Mohamed S. Abdel-Hamid,12 Ibrahim Hegazy,1 Ahmed G. Mohamed,13 Dominik T. Schneider,14 Aida Bertoli-Avella,15 Peter Bauer,15 Jillian N. Pearring,16,17 Rolph Pfundt,18 Alexander Hoischen,18,19 Christian Gilissen,18 Dennis Strand,20 Ulrich Zechner,4,21 Soha A. Tashkandi,22 Eissa A. Faqeih,23 Olaf Stemmann,2 Susanne Strand,20 and Hanno J. Bolz21,24

1Department of Clinical Genetics, Human Genetics and Genome Research Institute, National Research Centre, Cairo, Egypt.

2Chair of Genetics, University of Bayreuth, Bayreuth, Germany.

3Senckenberg Institute of Pathology, University Hospital Frankfurt, Frankfurt, Germany.

4Institute of Human Genetics, University Medical Center Mainz, Mainz, Germany.

5Human Cytogenetics Department, Human Genetics and Genome Research Institute, National Research Centre, Cairo, Egypt.

6Cologne Center for Genomics and

7Center for Molecular Medicine Cologne, University Hospital of Cologne, University of Cologne, Cologne, Germany.

8Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne, Germany.

9Paediatric Haematology/Oncology, Department of Paediatrics, University Hospital Tübingen, Tübingen, Germany.

10Institute of Medical Genetics and Applied Genomics, Eberhard-Karls University, Tübingen, Germany.

11Institute of Clinical Chemistry and Laboratory Medicine, University Medical Center Mainz, Mainz, Germany.

12Medical Molecular Department, Human Genetics and Genome Research Institute, National Research Centre, Cairo, Egypt.

13Pediatrics Department, Faculty of Medicine, Cairo University, Cairo, Egypt.

14Clinic of Pediatrics, University Witten/Herdecke, Dortmund, Germany.

15CENTOGENE GmbH, Rostock, Germany.

16Department of Ophthalmology and Visual Sciences and

17Department of Cell and Developmental Biology, University of Michigan School of Medicine, Ann Arbor, Michigan, USA.

18Department of Human Genetics and Radboud Institute for Molecular Life Sciences and

19Department of Internal Medicine, Radboud University Medical Center, Nijmegen, Netherlands.

20Department of Internal Medicine I, University Medical Center Mainz, Mainz, Germany.

21Senckenberg Centre for Human Genetics, Frankfurt am Main, Germany.

22Cytogenetics Laboratory, Pathology and Clinical Laboratory Medicine Administration (PCLMA), King Fahad Medical City, Second Central Healthcare Cluster (C2), Riyadh, Saudi Arabia.

23Section of Medical Genetics, Children’s Specialist Hospital, King Fahad Medical City, Riyadh, Saudi Arabia.

24Institute of Human Genetics, University Hospital of Cologne, University of Cologne, Cologne, Germany.

Address correspondence to: Hanno J. Bolz, Institute of Human Genetics, University Hospital of Cologne, Kerpener Str. 34, Cologne, Germany. Phone: 49.6132781206; Email: hanno.bolz@icloud.com.

Authorship note: GMHAS and SH contributed equally to this work. OS, SS, and HJB contributed equally to this work.

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1Department of Clinical Genetics, Human Genetics and Genome Research Institute, National Research Centre, Cairo, Egypt.

2Chair of Genetics, University of Bayreuth, Bayreuth, Germany.

3Senckenberg Institute of Pathology, University Hospital Frankfurt, Frankfurt, Germany.

4Institute of Human Genetics, University Medical Center Mainz, Mainz, Germany.

5Human Cytogenetics Department, Human Genetics and Genome Research Institute, National Research Centre, Cairo, Egypt.

6Cologne Center for Genomics and

7Center for Molecular Medicine Cologne, University Hospital of Cologne, University of Cologne, Cologne, Germany.

8Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne, Germany.

9Paediatric Haematology/Oncology, Department of Paediatrics, University Hospital Tübingen, Tübingen, Germany.

10Institute of Medical Genetics and Applied Genomics, Eberhard-Karls University, Tübingen, Germany.

11Institute of Clinical Chemistry and Laboratory Medicine, University Medical Center Mainz, Mainz, Germany.

12Medical Molecular Department, Human Genetics and Genome Research Institute, National Research Centre, Cairo, Egypt.

13Pediatrics Department, Faculty of Medicine, Cairo University, Cairo, Egypt.

14Clinic of Pediatrics, University Witten/Herdecke, Dortmund, Germany.

15CENTOGENE GmbH, Rostock, Germany.

16Department of Ophthalmology and Visual Sciences and

17Department of Cell and Developmental Biology, University of Michigan School of Medicine, Ann Arbor, Michigan, USA.

18Department of Human Genetics and Radboud Institute for Molecular Life Sciences and

19Department of Internal Medicine, Radboud University Medical Center, Nijmegen, Netherlands.

20Department of Internal Medicine I, University Medical Center Mainz, Mainz, Germany.

21Senckenberg Centre for Human Genetics, Frankfurt am Main, Germany.

22Cytogenetics Laboratory, Pathology and Clinical Laboratory Medicine Administration (PCLMA), King Fahad Medical City, Second Central Healthcare Cluster (C2), Riyadh, Saudi Arabia.

23Section of Medical Genetics, Children’s Specialist Hospital, King Fahad Medical City, Riyadh, Saudi Arabia.

24Institute of Human Genetics, University Hospital of Cologne, University of Cologne, Cologne, Germany.

Address correspondence to: Hanno J. Bolz, Institute of Human Genetics, University Hospital of Cologne, Kerpener Str. 34, Cologne, Germany. Phone: 49.6132781206; Email: hanno.bolz@icloud.com.

Authorship note: GMHAS and SH contributed equally to this work. OS, SS, and HJB contributed equally to this work.

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

1Department of Clinical Genetics, Human Genetics and Genome Research Institute, National Research Centre, Cairo, Egypt.

2Chair of Genetics, University of Bayreuth, Bayreuth, Germany.

3Senckenberg Institute of Pathology, University Hospital Frankfurt, Frankfurt, Germany.

4Institute of Human Genetics, University Medical Center Mainz, Mainz, Germany.

5Human Cytogenetics Department, Human Genetics and Genome Research Institute, National Research Centre, Cairo, Egypt.

6Cologne Center for Genomics and

7Center for Molecular Medicine Cologne, University Hospital of Cologne, University of Cologne, Cologne, Germany.

8Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne, Germany.

9Paediatric Haematology/Oncology, Department of Paediatrics, University Hospital Tübingen, Tübingen, Germany.

10Institute of Medical Genetics and Applied Genomics, Eberhard-Karls University, Tübingen, Germany.

11Institute of Clinical Chemistry and Laboratory Medicine, University Medical Center Mainz, Mainz, Germany.

12Medical Molecular Department, Human Genetics and Genome Research Institute, National Research Centre, Cairo, Egypt.

13Pediatrics Department, Faculty of Medicine, Cairo University, Cairo, Egypt.

14Clinic of Pediatrics, University Witten/Herdecke, Dortmund, Germany.

15CENTOGENE GmbH, Rostock, Germany.

16Department of Ophthalmology and Visual Sciences and

17Department of Cell and Developmental Biology, University of Michigan School of Medicine, Ann Arbor, Michigan, USA.

18Department of Human Genetics and Radboud Institute for Molecular Life Sciences and

19Department of Internal Medicine, Radboud University Medical Center, Nijmegen, Netherlands.

20Department of Internal Medicine I, University Medical Center Mainz, Mainz, Germany.

21Senckenberg Centre for Human Genetics, Frankfurt am Main, Germany.

22Cytogenetics Laboratory, Pathology and Clinical Laboratory Medicine Administration (PCLMA), King Fahad Medical City, Second Central Healthcare Cluster (C2), Riyadh, Saudi Arabia.

23Section of Medical Genetics, Children’s Specialist Hospital, King Fahad Medical City, Riyadh, Saudi Arabia.

24Institute of Human Genetics, University Hospital of Cologne, University of Cologne, Cologne, Germany.

Address correspondence to: Hanno J. Bolz, Institute of Human Genetics, University Hospital of Cologne, Kerpener Str. 34, Cologne, Germany. Phone: 49.6132781206; Email: hanno.bolz@icloud.com.

Authorship note: GMHAS and SH contributed equally to this work. OS, SS, and HJB contributed equally to this work.

Find articles by Gradhand, E. in: JCI | PubMed | Google Scholar

1Department of Clinical Genetics, Human Genetics and Genome Research Institute, National Research Centre, Cairo, Egypt.

2Chair of Genetics, University of Bayreuth, Bayreuth, Germany.

3Senckenberg Institute of Pathology, University Hospital Frankfurt, Frankfurt, Germany.

4Institute of Human Genetics, University Medical Center Mainz, Mainz, Germany.

5Human Cytogenetics Department, Human Genetics and Genome Research Institute, National Research Centre, Cairo, Egypt.

6Cologne Center for Genomics and

7Center for Molecular Medicine Cologne, University Hospital of Cologne, University of Cologne, Cologne, Germany.

8Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne, Germany.

9Paediatric Haematology/Oncology, Department of Paediatrics, University Hospital Tübingen, Tübingen, Germany.

10Institute of Medical Genetics and Applied Genomics, Eberhard-Karls University, Tübingen, Germany.

11Institute of Clinical Chemistry and Laboratory Medicine, University Medical Center Mainz, Mainz, Germany.

12Medical Molecular Department, Human Genetics and Genome Research Institute, National Research Centre, Cairo, Egypt.

13Pediatrics Department, Faculty of Medicine, Cairo University, Cairo, Egypt.

14Clinic of Pediatrics, University Witten/Herdecke, Dortmund, Germany.

15CENTOGENE GmbH, Rostock, Germany.

16Department of Ophthalmology and Visual Sciences and

17Department of Cell and Developmental Biology, University of Michigan School of Medicine, Ann Arbor, Michigan, USA.

18Department of Human Genetics and Radboud Institute for Molecular Life Sciences and

19Department of Internal Medicine, Radboud University Medical Center, Nijmegen, Netherlands.

20Department of Internal Medicine I, University Medical Center Mainz, Mainz, Germany.

21Senckenberg Centre for Human Genetics, Frankfurt am Main, Germany.

22Cytogenetics Laboratory, Pathology and Clinical Laboratory Medicine Administration (PCLMA), King Fahad Medical City, Second Central Healthcare Cluster (C2), Riyadh, Saudi Arabia.

23Section of Medical Genetics, Children’s Specialist Hospital, King Fahad Medical City, Riyadh, Saudi Arabia.

24Institute of Human Genetics, University Hospital of Cologne, University of Cologne, Cologne, Germany.

Address correspondence to: Hanno J. Bolz, Institute of Human Genetics, University Hospital of Cologne, Kerpener Str. 34, Cologne, Germany. Phone: 49.6132781206; Email: hanno.bolz@icloud.com.

Authorship note: GMHAS and SH contributed equally to this work. OS, SS, and HJB contributed equally to this work.

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

1Department of Clinical Genetics, Human Genetics and Genome Research Institute, National Research Centre, Cairo, Egypt.

2Chair of Genetics, University of Bayreuth, Bayreuth, Germany.

3Senckenberg Institute of Pathology, University Hospital Frankfurt, Frankfurt, Germany.

4Institute of Human Genetics, University Medical Center Mainz, Mainz, Germany.

5Human Cytogenetics Department, Human Genetics and Genome Research Institute, National Research Centre, Cairo, Egypt.

6Cologne Center for Genomics and

7Center for Molecular Medicine Cologne, University Hospital of Cologne, University of Cologne, Cologne, Germany.

8Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne, Germany.

9Paediatric Haematology/Oncology, Department of Paediatrics, University Hospital Tübingen, Tübingen, Germany.

10Institute of Medical Genetics and Applied Genomics, Eberhard-Karls University, Tübingen, Germany.

11Institute of Clinical Chemistry and Laboratory Medicine, University Medical Center Mainz, Mainz, Germany.

12Medical Molecular Department, Human Genetics and Genome Research Institute, National Research Centre, Cairo, Egypt.

13Pediatrics Department, Faculty of Medicine, Cairo University, Cairo, Egypt.

14Clinic of Pediatrics, University Witten/Herdecke, Dortmund, Germany.

15CENTOGENE GmbH, Rostock, Germany.

16Department of Ophthalmology and Visual Sciences and

17Department of Cell and Developmental Biology, University of Michigan School of Medicine, Ann Arbor, Michigan, USA.

18Department of Human Genetics and Radboud Institute for Molecular Life Sciences and

19Department of Internal Medicine, Radboud University Medical Center, Nijmegen, Netherlands.

20Department of Internal Medicine I, University Medical Center Mainz, Mainz, Germany.

21Senckenberg Centre for Human Genetics, Frankfurt am Main, Germany.

22Cytogenetics Laboratory, Pathology and Clinical Laboratory Medicine Administration (PCLMA), King Fahad Medical City, Second Central Healthcare Cluster (C2), Riyadh, Saudi Arabia.

23Section of Medical Genetics, Children’s Specialist Hospital, King Fahad Medical City, Riyadh, Saudi Arabia.

24Institute of Human Genetics, University Hospital of Cologne, University of Cologne, Cologne, Germany.

Address correspondence to: Hanno J. Bolz, Institute of Human Genetics, University Hospital of Cologne, Kerpener Str. 34, Cologne, Germany. Phone: 49.6132781206; Email: hanno.bolz@icloud.com.

Authorship note: GMHAS and SH contributed equally to this work. OS, SS, and HJB contributed equally to this work.

Find articles by Winter, J. in: JCI | PubMed | Google Scholar

1Department of Clinical Genetics, Human Genetics and Genome Research Institute, National Research Centre, Cairo, Egypt.

2Chair of Genetics, University of Bayreuth, Bayreuth, Germany.

3Senckenberg Institute of Pathology, University Hospital Frankfurt, Frankfurt, Germany.

4Institute of Human Genetics, University Medical Center Mainz, Mainz, Germany.

5Human Cytogenetics Department, Human Genetics and Genome Research Institute, National Research Centre, Cairo, Egypt.

6Cologne Center for Genomics and

7Center for Molecular Medicine Cologne, University Hospital of Cologne, University of Cologne, Cologne, Germany.

8Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne, Germany.

9Paediatric Haematology/Oncology, Department of Paediatrics, University Hospital Tübingen, Tübingen, Germany.

10Institute of Medical Genetics and Applied Genomics, Eberhard-Karls University, Tübingen, Germany.

11Institute of Clinical Chemistry and Laboratory Medicine, University Medical Center Mainz, Mainz, Germany.

12Medical Molecular Department, Human Genetics and Genome Research Institute, National Research Centre, Cairo, Egypt.

13Pediatrics Department, Faculty of Medicine, Cairo University, Cairo, Egypt.

14Clinic of Pediatrics, University Witten/Herdecke, Dortmund, Germany.

15CENTOGENE GmbH, Rostock, Germany.

16Department of Ophthalmology and Visual Sciences and

17Department of Cell and Developmental Biology, University of Michigan School of Medicine, Ann Arbor, Michigan, USA.

18Department of Human Genetics and Radboud Institute for Molecular Life Sciences and

19Department of Internal Medicine, Radboud University Medical Center, Nijmegen, Netherlands.

20Department of Internal Medicine I, University Medical Center Mainz, Mainz, Germany.

21Senckenberg Centre for Human Genetics, Frankfurt am Main, Germany.

22Cytogenetics Laboratory, Pathology and Clinical Laboratory Medicine Administration (PCLMA), King Fahad Medical City, Second Central Healthcare Cluster (C2), Riyadh, Saudi Arabia.

23Section of Medical Genetics, Children’s Specialist Hospital, King Fahad Medical City, Riyadh, Saudi Arabia.

24Institute of Human Genetics, University Hospital of Cologne, University of Cologne, Cologne, Germany.

Address correspondence to: Hanno J. Bolz, Institute of Human Genetics, University Hospital of Cologne, Kerpener Str. 34, Cologne, Germany. Phone: 49.6132781206; Email: hanno.bolz@icloud.com.

Authorship note: GMHAS and SH contributed equally to this work. OS, SS, and HJB contributed equally to this work.

Find articles by Pabst, A. in: JCI | PubMed | Google Scholar

1Department of Clinical Genetics, Human Genetics and Genome Research Institute, National Research Centre, Cairo, Egypt.

2Chair of Genetics, University of Bayreuth, Bayreuth, Germany.

3Senckenberg Institute of Pathology, University Hospital Frankfurt, Frankfurt, Germany.

4Institute of Human Genetics, University Medical Center Mainz, Mainz, Germany.

5Human Cytogenetics Department, Human Genetics and Genome Research Institute, National Research Centre, Cairo, Egypt.

6Cologne Center for Genomics and

7Center for Molecular Medicine Cologne, University Hospital of Cologne, University of Cologne, Cologne, Germany.

8Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne, Germany.

9Paediatric Haematology/Oncology, Department of Paediatrics, University Hospital Tübingen, Tübingen, Germany.

10Institute of Medical Genetics and Applied Genomics, Eberhard-Karls University, Tübingen, Germany.

11Institute of Clinical Chemistry and Laboratory Medicine, University Medical Center Mainz, Mainz, Germany.

12Medical Molecular Department, Human Genetics and Genome Research Institute, National Research Centre, Cairo, Egypt.

13Pediatrics Department, Faculty of Medicine, Cairo University, Cairo, Egypt.

14Clinic of Pediatrics, University Witten/Herdecke, Dortmund, Germany.

15CENTOGENE GmbH, Rostock, Germany.

16Department of Ophthalmology and Visual Sciences and

17Department of Cell and Developmental Biology, University of Michigan School of Medicine, Ann Arbor, Michigan, USA.

18Department of Human Genetics and Radboud Institute for Molecular Life Sciences and

19Department of Internal Medicine, Radboud University Medical Center, Nijmegen, Netherlands.

20Department of Internal Medicine I, University Medical Center Mainz, Mainz, Germany.

21Senckenberg Centre for Human Genetics, Frankfurt am Main, Germany.

22Cytogenetics Laboratory, Pathology and Clinical Laboratory Medicine Administration (PCLMA), King Fahad Medical City, Second Central Healthcare Cluster (C2), Riyadh, Saudi Arabia.

23Section of Medical Genetics, Children’s Specialist Hospital, King Fahad Medical City, Riyadh, Saudi Arabia.

24Institute of Human Genetics, University Hospital of Cologne, University of Cologne, Cologne, Germany.

Address correspondence to: Hanno J. Bolz, Institute of Human Genetics, University Hospital of Cologne, Kerpener Str. 34, Cologne, Germany. Phone: 49.6132781206; Email: hanno.bolz@icloud.com.

Authorship note: GMHAS and SH contributed equally to this work. OS, SS, and HJB contributed equally to this work.

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

1Department of Clinical Genetics, Human Genetics and Genome Research Institute, National Research Centre, Cairo, Egypt.

2Chair of Genetics, University of Bayreuth, Bayreuth, Germany.

3Senckenberg Institute of Pathology, University Hospital Frankfurt, Frankfurt, Germany.

4Institute of Human Genetics, University Medical Center Mainz, Mainz, Germany.

5Human Cytogenetics Department, Human Genetics and Genome Research Institute, National Research Centre, Cairo, Egypt.

6Cologne Center for Genomics and

7Center for Molecular Medicine Cologne, University Hospital of Cologne, University of Cologne, Cologne, Germany.

8Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne, Germany.

9Paediatric Haematology/Oncology, Department of Paediatrics, University Hospital Tübingen, Tübingen, Germany.

10Institute of Medical Genetics and Applied Genomics, Eberhard-Karls University, Tübingen, Germany.

11Institute of Clinical Chemistry and Laboratory Medicine, University Medical Center Mainz, Mainz, Germany.

12Medical Molecular Department, Human Genetics and Genome Research Institute, National Research Centre, Cairo, Egypt.

13Pediatrics Department, Faculty of Medicine, Cairo University, Cairo, Egypt.

14Clinic of Pediatrics, University Witten/Herdecke, Dortmund, Germany.

15CENTOGENE GmbH, Rostock, Germany.

16Department of Ophthalmology and Visual Sciences and

17Department of Cell and Developmental Biology, University of Michigan School of Medicine, Ann Arbor, Michigan, USA.

18Department of Human Genetics and Radboud Institute for Molecular Life Sciences and

19Department of Internal Medicine, Radboud University Medical Center, Nijmegen, Netherlands.

20Department of Internal Medicine I, University Medical Center Mainz, Mainz, Germany.

21Senckenberg Centre for Human Genetics, Frankfurt am Main, Germany.

22Cytogenetics Laboratory, Pathology and Clinical Laboratory Medicine Administration (PCLMA), King Fahad Medical City, Second Central Healthcare Cluster (C2), Riyadh, Saudi Arabia.

23Section of Medical Genetics, Children’s Specialist Hospital, King Fahad Medical City, Riyadh, Saudi Arabia.

24Institute of Human Genetics, University Hospital of Cologne, University of Cologne, Cologne, Germany.

Address correspondence to: Hanno J. Bolz, Institute of Human Genetics, University Hospital of Cologne, Kerpener Str. 34, Cologne, Germany. Phone: 49.6132781206; Email: hanno.bolz@icloud.com.

Authorship note: GMHAS and SH contributed equally to this work. OS, SS, and HJB contributed equally to this work.

Find articles by Thiele, H. in: JCI | PubMed | Google Scholar |

1Department of Clinical Genetics, Human Genetics and Genome Research Institute, National Research Centre, Cairo, Egypt.

2Chair of Genetics, University of Bayreuth, Bayreuth, Germany.

3Senckenberg Institute of Pathology, University Hospital Frankfurt, Frankfurt, Germany.

4Institute of Human Genetics, University Medical Center Mainz, Mainz, Germany.

5Human Cytogenetics Department, Human Genetics and Genome Research Institute, National Research Centre, Cairo, Egypt.

6Cologne Center for Genomics and

7Center for Molecular Medicine Cologne, University Hospital of Cologne, University of Cologne, Cologne, Germany.

8Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne, Germany.

9Paediatric Haematology/Oncology, Department of Paediatrics, University Hospital Tübingen, Tübingen, Germany.

10Institute of Medical Genetics and Applied Genomics, Eberhard-Karls University, Tübingen, Germany.

11Institute of Clinical Chemistry and Laboratory Medicine, University Medical Center Mainz, Mainz, Germany.

12Medical Molecular Department, Human Genetics and Genome Research Institute, National Research Centre, Cairo, Egypt.

13Pediatrics Department, Faculty of Medicine, Cairo University, Cairo, Egypt.

14Clinic of Pediatrics, University Witten/Herdecke, Dortmund, Germany.

15CENTOGENE GmbH, Rostock, Germany.

16Department of Ophthalmology and Visual Sciences and

17Department of Cell and Developmental Biology, University of Michigan School of Medicine, Ann Arbor, Michigan, USA.

18Department of Human Genetics and Radboud Institute for Molecular Life Sciences and

19Department of Internal Medicine, Radboud University Medical Center, Nijmegen, Netherlands.

20Department of Internal Medicine I, University Medical Center Mainz, Mainz, Germany.

21Senckenberg Centre for Human Genetics, Frankfurt am Main, Germany.

22Cytogenetics Laboratory, Pathology and Clinical Laboratory Medicine Administration (PCLMA), King Fahad Medical City, Second Central Healthcare Cluster (C2), Riyadh, Saudi Arabia.

23Section of Medical Genetics, Children’s Specialist Hospital, King Fahad Medical City, Riyadh, Saudi Arabia.

24Institute of Human Genetics, University Hospital of Cologne, University of Cologne, Cologne, Germany.

Address correspondence to: Hanno J. Bolz, Institute of Human Genetics, University Hospital of Cologne, Kerpener Str. 34, Cologne, Germany. Phone: 49.6132781206; Email: hanno.bolz@icloud.com.

Authorship note: GMHAS and SH contributed equally to this work. OS, SS, and HJB contributed equally to this work.

Find articles by Nürnberg, P. in: JCI | PubMed | Google Scholar |

1Department of Clinical Genetics, Human Genetics and Genome Research Institute, National Research Centre, Cairo, Egypt.

2Chair of Genetics, University of Bayreuth, Bayreuth, Germany.

3Senckenberg Institute of Pathology, University Hospital Frankfurt, Frankfurt, Germany.

4Institute of Human Genetics, University Medical Center Mainz, Mainz, Germany.

5Human Cytogenetics Department, Human Genetics and Genome Research Institute, National Research Centre, Cairo, Egypt.

6Cologne Center for Genomics and

7Center for Molecular Medicine Cologne, University Hospital of Cologne, University of Cologne, Cologne, Germany.

8Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne, Germany.

9Paediatric Haematology/Oncology, Department of Paediatrics, University Hospital Tübingen, Tübingen, Germany.

10Institute of Medical Genetics and Applied Genomics, Eberhard-Karls University, Tübingen, Germany.

11Institute of Clinical Chemistry and Laboratory Medicine, University Medical Center Mainz, Mainz, Germany.

12Medical Molecular Department, Human Genetics and Genome Research Institute, National Research Centre, Cairo, Egypt.

13Pediatrics Department, Faculty of Medicine, Cairo University, Cairo, Egypt.

14Clinic of Pediatrics, University Witten/Herdecke, Dortmund, Germany.

15CENTOGENE GmbH, Rostock, Germany.

16Department of Ophthalmology and Visual Sciences and

17Department of Cell and Developmental Biology, University of Michigan School of Medicine, Ann Arbor, Michigan, USA.

18Department of Human Genetics and Radboud Institute for Molecular Life Sciences and

19Department of Internal Medicine, Radboud University Medical Center, Nijmegen, Netherlands.

20Department of Internal Medicine I, University Medical Center Mainz, Mainz, Germany.

21Senckenberg Centre for Human Genetics, Frankfurt am Main, Germany.

22Cytogenetics Laboratory, Pathology and Clinical Laboratory Medicine Administration (PCLMA), King Fahad Medical City, Second Central Healthcare Cluster (C2), Riyadh, Saudi Arabia.

23Section of Medical Genetics, Children’s Specialist Hospital, King Fahad Medical City, Riyadh, Saudi Arabia.

24Institute of Human Genetics, University Hospital of Cologne, University of Cologne, Cologne, Germany.

Address correspondence to: Hanno J. Bolz, Institute of Human Genetics, University Hospital of Cologne, Kerpener Str. 34, Cologne, Germany. Phone: 49.6132781206; Email: hanno.bolz@icloud.com.

Authorship note: GMHAS and SH contributed equally to this work. OS, SS, and HJB contributed equally to this work.

Find articles by Budde, B. in: JCI | PubMed | Google Scholar

1Department of Clinical Genetics, Human Genetics and Genome Research Institute, National Research Centre, Cairo, Egypt.

2Chair of Genetics, University of Bayreuth, Bayreuth, Germany.

3Senckenberg Institute of Pathology, University Hospital Frankfurt, Frankfurt, Germany.

4Institute of Human Genetics, University Medical Center Mainz, Mainz, Germany.

5Human Cytogenetics Department, Human Genetics and Genome Research Institute, National Research Centre, Cairo, Egypt.

6Cologne Center for Genomics and

7Center for Molecular Medicine Cologne, University Hospital of Cologne, University of Cologne, Cologne, Germany.

8Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne, Germany.

9Paediatric Haematology/Oncology, Department of Paediatrics, University Hospital Tübingen, Tübingen, Germany.

10Institute of Medical Genetics and Applied Genomics, Eberhard-Karls University, Tübingen, Germany.

11Institute of Clinical Chemistry and Laboratory Medicine, University Medical Center Mainz, Mainz, Germany.

12Medical Molecular Department, Human Genetics and Genome Research Institute, National Research Centre, Cairo, Egypt.

13Pediatrics Department, Faculty of Medicine, Cairo University, Cairo, Egypt.

14Clinic of Pediatrics, University Witten/Herdecke, Dortmund, Germany.

15CENTOGENE GmbH, Rostock, Germany.

16Department of Ophthalmology and Visual Sciences and

17Department of Cell and Developmental Biology, University of Michigan School of Medicine, Ann Arbor, Michigan, USA.

18Department of Human Genetics and Radboud Institute for Molecular Life Sciences and

19Department of Internal Medicine, Radboud University Medical Center, Nijmegen, Netherlands.

20Department of Internal Medicine I, University Medical Center Mainz, Mainz, Germany.

21Senckenberg Centre for Human Genetics, Frankfurt am Main, Germany.

22Cytogenetics Laboratory, Pathology and Clinical Laboratory Medicine Administration (PCLMA), King Fahad Medical City, Second Central Healthcare Cluster (C2), Riyadh, Saudi Arabia.

23Section of Medical Genetics, Children’s Specialist Hospital, King Fahad Medical City, Riyadh, Saudi Arabia.

24Institute of Human Genetics, University Hospital of Cologne, University of Cologne, Cologne, Germany.

Address correspondence to: Hanno J. Bolz, Institute of Human Genetics, University Hospital of Cologne, Kerpener Str. 34, Cologne, Germany. Phone: 49.6132781206; Email: hanno.bolz@icloud.com.

Authorship note: GMHAS and SH contributed equally to this work. OS, SS, and HJB contributed equally to this work.

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

1Department of Clinical Genetics, Human Genetics and Genome Research Institute, National Research Centre, Cairo, Egypt.

2Chair of Genetics, University of Bayreuth, Bayreuth, Germany.

3Senckenberg Institute of Pathology, University Hospital Frankfurt, Frankfurt, Germany.

4Institute of Human Genetics, University Medical Center Mainz, Mainz, Germany.

5Human Cytogenetics Department, Human Genetics and Genome Research Institute, National Research Centre, Cairo, Egypt.

6Cologne Center for Genomics and

7Center for Molecular Medicine Cologne, University Hospital of Cologne, University of Cologne, Cologne, Germany.

8Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne, Germany.

9Paediatric Haematology/Oncology, Department of Paediatrics, University Hospital Tübingen, Tübingen, Germany.

10Institute of Medical Genetics and Applied Genomics, Eberhard-Karls University, Tübingen, Germany.

11Institute of Clinical Chemistry and Laboratory Medicine, University Medical Center Mainz, Mainz, Germany.

12Medical Molecular Department, Human Genetics and Genome Research Institute, National Research Centre, Cairo, Egypt.

13Pediatrics Department, Faculty of Medicine, Cairo University, Cairo, Egypt.

14Clinic of Pediatrics, University Witten/Herdecke, Dortmund, Germany.

15CENTOGENE GmbH, Rostock, Germany.

16Department of Ophthalmology and Visual Sciences and

17Department of Cell and Developmental Biology, University of Michigan School of Medicine, Ann Arbor, Michigan, USA.

18Department of Human Genetics and Radboud Institute for Molecular Life Sciences and

19Department of Internal Medicine, Radboud University Medical Center, Nijmegen, Netherlands.

20Department of Internal Medicine I, University Medical Center Mainz, Mainz, Germany.

21Senckenberg Centre for Human Genetics, Frankfurt am Main, Germany.

22Cytogenetics Laboratory, Pathology and Clinical Laboratory Medicine Administration (PCLMA), King Fahad Medical City, Second Central Healthcare Cluster (C2), Riyadh, Saudi Arabia.

23Section of Medical Genetics, Children’s Specialist Hospital, King Fahad Medical City, Riyadh, Saudi Arabia.

24Institute of Human Genetics, University Hospital of Cologne, University of Cologne, Cologne, Germany.

Address correspondence to: Hanno J. Bolz, Institute of Human Genetics, University Hospital of Cologne, Kerpener Str. 34, Cologne, Germany. Phone: 49.6132781206; Email: hanno.bolz@icloud.com.

Authorship note: GMHAS and SH contributed equally to this work. OS, SS, and HJB contributed equally to this work.

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1Department of Clinical Genetics, Human Genetics and Genome Research Institute, National Research Centre, Cairo, Egypt.

2Chair of Genetics, University of Bayreuth, Bayreuth, Germany.

3Senckenberg Institute of Pathology, University Hospital Frankfurt, Frankfurt, Germany.

4Institute of Human Genetics, University Medical Center Mainz, Mainz, Germany.

5Human Cytogenetics Department, Human Genetics and Genome Research Institute, National Research Centre, Cairo, Egypt.

6Cologne Center for Genomics and

7Center for Molecular Medicine Cologne, University Hospital of Cologne, University of Cologne, Cologne, Germany.

8Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne, Germany.

9Paediatric Haematology/Oncology, Department of Paediatrics, University Hospital Tübingen, Tübingen, Germany.

10Institute of Medical Genetics and Applied Genomics, Eberhard-Karls University, Tübingen, Germany.

11Institute of Clinical Chemistry and Laboratory Medicine, University Medical Center Mainz, Mainz, Germany.

12Medical Molecular Department, Human Genetics and Genome Research Institute, National Research Centre, Cairo, Egypt.

13Pediatrics Department, Faculty of Medicine, Cairo University, Cairo, Egypt.

14Clinic of Pediatrics, University Witten/Herdecke, Dortmund, Germany.

15CENTOGENE GmbH, Rostock, Germany.

16Department of Ophthalmology and Visual Sciences and

17Department of Cell and Developmental Biology, University of Michigan School of Medicine, Ann Arbor, Michigan, USA.

18Department of Human Genetics and Radboud Institute for Molecular Life Sciences and

19Department of Internal Medicine, Radboud University Medical Center, Nijmegen, Netherlands.

20Department of Internal Medicine I, University Medical Center Mainz, Mainz, Germany.

21Senckenberg Centre for Human Genetics, Frankfurt am Main, Germany.

22Cytogenetics Laboratory, Pathology and Clinical Laboratory Medicine Administration (PCLMA), King Fahad Medical City, Second Central Healthcare Cluster (C2), Riyadh, Saudi Arabia.

23Section of Medical Genetics, Children’s Specialist Hospital, King Fahad Medical City, Riyadh, Saudi Arabia.

24Institute of Human Genetics, University Hospital of Cologne, University of Cologne, Cologne, Germany.

Address correspondence to: Hanno J. Bolz, Institute of Human Genetics, University Hospital of Cologne, Kerpener Str. 34, Cologne, Germany. Phone: 49.6132781206; Email: hanno.bolz@icloud.com.

Authorship note: GMHAS and SH contributed equally to this work. OS, SS, and HJB contributed equally to this work.

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1Department of Clinical Genetics, Human Genetics and Genome Research Institute, National Research Centre, Cairo, Egypt.

2Chair of Genetics, University of Bayreuth, Bayreuth, Germany.

3Senckenberg Institute of Pathology, University Hospital Frankfurt, Frankfurt, Germany.

4Institute of Human Genetics, University Medical Center Mainz, Mainz, Germany.

5Human Cytogenetics Department, Human Genetics and Genome Research Institute, National Research Centre, Cairo, Egypt.

6Cologne Center for Genomics and

7Center for Molecular Medicine Cologne, University Hospital of Cologne, University of Cologne, Cologne, Germany.

8Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne, Germany.

9Paediatric Haematology/Oncology, Department of Paediatrics, University Hospital Tübingen, Tübingen, Germany.

10Institute of Medical Genetics and Applied Genomics, Eberhard-Karls University, Tübingen, Germany.

11Institute of Clinical Chemistry and Laboratory Medicine, University Medical Center Mainz, Mainz, Germany.

12Medical Molecular Department, Human Genetics and Genome Research Institute, National Research Centre, Cairo, Egypt.

13Pediatrics Department, Faculty of Medicine, Cairo University, Cairo, Egypt.

14Clinic of Pediatrics, University Witten/Herdecke, Dortmund, Germany.

15CENTOGENE GmbH, Rostock, Germany.

16Department of Ophthalmology and Visual Sciences and

17Department of Cell and Developmental Biology, University of Michigan School of Medicine, Ann Arbor, Michigan, USA.

18Department of Human Genetics and Radboud Institute for Molecular Life Sciences and

19Department of Internal Medicine, Radboud University Medical Center, Nijmegen, Netherlands.

20Department of Internal Medicine I, University Medical Center Mainz, Mainz, Germany.

21Senckenberg Centre for Human Genetics, Frankfurt am Main, Germany.

22Cytogenetics Laboratory, Pathology and Clinical Laboratory Medicine Administration (PCLMA), King Fahad Medical City, Second Central Healthcare Cluster (C2), Riyadh, Saudi Arabia.

23Section of Medical Genetics, Children’s Specialist Hospital, King Fahad Medical City, Riyadh, Saudi Arabia.

24Institute of Human Genetics, University Hospital of Cologne, University of Cologne, Cologne, Germany.

Address correspondence to: Hanno J. Bolz, Institute of Human Genetics, University Hospital of Cologne, Kerpener Str. 34, Cologne, Germany. Phone: 49.6132781206; Email: hanno.bolz@icloud.com.

Authorship note: GMHAS and SH contributed equally to this work. OS, SS, and HJB contributed equally to this work.

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