Whole-exome sequencing identifies recessive WDR62 mutations in severe brain malformations (original) (raw)

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Acknowledgements

We are indebted to the patients and families who have contributed to this study. We thank J. Noonan for expert advice and C. Camputaro for her help with three-dimensional reconstruction of the magnetic resonance images. This study was supported by the Yale Program on Neurogenetics, the Yale Center for Human Genetics and Genomics, and National Institutes of Health grants RC2 NS070477 (to M.G.), UL1 RR024139NIH (Yale Clinical and Translational Science Award) and UO1MH081896 (to N.S.). SNP genotyping was supported in part by a National Institutes of Health Neuroscience Microarray Consortium award U24 NS051869-02S1 (to S.M.). R.P.L. is an investigator of the Howard Hughes Medical Institute.

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Author notes

1. Kaya Bilgüvar and Ali Kemal Öztürk: These authors contributed equally to this work.

Authors and Affiliations

1. Department of Neurosurgery, Yale University School of Medicine, New Haven, 06510, Connecticut, USA
   Kaya Bilgüvar, Ali Kemal Öztürk, Angeliki Louvi, Tanyeri Barak, Mehmet Bakırcıoğlu, Katsuhito Yasuno, Winson Ho, Michele H. Johnson, Richard A. Bronen & Murat Günel
2. Department of Neurobiology, Yale University School of Medicine, New Haven, 06510, Connecticut, USA
   Kaya Bilgüvar, Ali Kemal Öztürk, Angeliki Louvi, Kenneth Y. Kwan, Tanyeri Barak, Mehmet Bakırcıoğlu, Katsuhito Yasuno, Winson Ho, Ying Zhu, Nenad Šestan & Murat Günel
3. Department of Genetics, Center for Human Genetics and Genomics and Program on Neurogenetics, Yale University School of Medicine, New Haven, 06510, Connecticut, USA
   Kaya Bilgüvar, Ali Kemal Öztürk, Angeliki Louvi, Murim Choi, Tanyeri Barak, Mehmet Bakırcıoğlu, Katsuhito Yasuno, Winson Ho, Stephan Sanders, Shrikant Mane, Richard P. Lifton, Matthew W. State & Murat Günel
4. Kavli Institute for Neuroscience, Yale University School of Medicine, New Haven, 06510, Connecticut, USA
   Kenneth Y. Kwan, Ying Zhu & Nenad Šestan
5. Division of Neurology, Department of Pediatrics, Istanbul University Istanbul Medical Faculty, Istanbul, 34093, Turkey
   Burak Tatlı & Meral Özmen
6. Division of Neurology, Department of Pediatrics, Hacettepe University School of Medicine, Sihhiye, 06100, Ankara, Turkey
   Dilek Yalnızoğlu & Meral Topçu
7. Division of Genetics, Department of Pediatrics, Istanbul University Cerrahpasa Faculty of Medicine, Istanbul, 34098, Turkey
   Beyhan Tüysüz
8. Department of Medical Genetics, Kayseri Education and Research Hospital, Kayseri, 38010, Turkey
   Ahmet Okay Çağlayan
9. Division of Neurology, Department of Pediatrics, Ege University Faculty of Medicine, Izmir, 35100, Turkey
   Sarenur Gökben & Sanem Yılmaz
10. Faculty of Arts and Sciences, Bahcesehir University, Istanbul, 34353, Turkey
    Hande Kaymakçalan
11. Department of Psychiatry, Yale University School of Medicine, New Haven, 06510, Connecticut, USA
    Stephan Sanders & Matthew W. State
12. Child Study Center, Yale University School of Medicine, New Haven, 06510, Connecticut, USA
    Stephan Sanders & Matthew W. State
13. Department of Radiology, Acibadem University School of Medicine, Istanbul, 34742, Turkey
    Alp Dinçer
14. Department of Radiology, Yale University School of Medicine, New Haven, 06510, Connecticut, USA
    Michele H. Johnson & Richard A. Bronen
15. Department of Otolaryngology, Yale University School of Medicine, New Haven, 06510, Connecticut, USA
    Michele H. Johnson
16. Department of Radiology, Istanbul University Cerrahpasa Faculty of Medicine, Istanbul, 34098, Turkey
    Naci Koçer
17. Division of Neurology, Department of Pediatrics, Erciyes University School of Medicine, Kayseri, 38039, Turkey
    Hüseyin Per & Sefer Kumandaş
18. Yale Center for Genome Analysis, Yale University School of Medicine, New Haven, 06510, Connecticut, USA
    Shrikant Mane
19. Department of Neurosurgery, Acibadem University School of Medicine, Istanbul, 34742, Turkey
    Mehmet Necmettin Pamir
20. Division of Child Neurology, Department of Neurology, Istanbul University Cerrahpasa Faculty of Medicine, Istanbul, 34098, Turkey
    Cengiz Yalçınkaya
21. Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, 06510, Connecticut, USA
    Richard P. Lifton

Authors

1. Kaya Bilgüvar
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2. Ali Kemal Öztürk
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3. Angeliki Louvi
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4. Kenneth Y. Kwan
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5. Murim Choi
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6. Burak Tatlı
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7. Dilek Yalnızoğlu
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8. Beyhan Tüysüz
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9. Ahmet Okay Çağlayan
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10. Sarenur Gökben
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11. Hande Kaymakçalan
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12. Tanyeri Barak
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13. Mehmet Bakırcıoğlu
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14. Katsuhito Yasuno
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15. Winson Ho
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16. Stephan Sanders
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17. Ying Zhu
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18. Sanem Yılmaz
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19. Alp Dinçer
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20. Michele H. Johnson
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21. Richard A. Bronen
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22. Naci Koçer
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23. Hüseyin Per
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24. Shrikant Mane
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25. Mehmet Necmettin Pamir
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26. Cengiz Yalçınkaya
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27. Sefer Kumandaş
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28. Meral Topçu
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29. Meral Özmen
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30. Nenad Šestan
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31. Richard P. Lifton
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32. Matthew W. State
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33. Murat Günel
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Contributions

M.W.S., R.P.L. and M.G. designed the study and K.B., A.L., N.S., R.P.L. and M.G. designed the experiments. K.B., A.K.O., A.L., K.Y.K., T.B., M.B., S.S., W.H. and S.M. performed the experiments. B.T., D.Y., B.T., A.O.C., S.G., H.K., S.Y., H.P., C.Y., S.K., M.T. and M.O. identified, consented and recruited the study subjects and provided clinical information. A.D., M.H.J., R.A.B., N.K. and M.N.P. performed and evaluated magnetic resonance imaging. M.C. and R.P.L. developed the bioinformatics scripts for data analysis. K.B., A.K.O., K.Y., A.L. and M.G. analysed the genetics data. A.L., K.Y.K, Y.Z., N.S. and M.G. analysed the expression data. K.B., A.K.O, A.L., R.P.L., M.W.S. and M.G. wrote the paper.

Corresponding authors

Correspondence toRichard P. Lifton, Matthew W. State or Murat Günel.

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Competing interests

The authors have a provisional patent application under consideration based on the findings of this work. R.A.B. is a consultant for Bristol-Myers Squibb.

Supplementary information

Supplementary Information

This file contains Supplementary Patient Notes, legends for Supplementary Videos 1- 6 (see separate Movie files 1-6), Supplementary Figures 1-8 with legends and Supplementary Tables 1-6. (PDF 2092 kb)

Supplementary Movie 1

This video is constructed from T2 sagittal images (photographically inverted) of patient NG 26-1 and demonstrates microcephaly and cortical thickening (see Supplementary Information file for full legend). (MOV 4003 kb)

Supplementary Movie 2

This video is constructed from T2 coronal images (photographically inverted) of patient NG 26-1 and demonstrates microcephaly and cortical thickening (see Supplementary Information file for full legend). (MOV 3620 kb)

Supplementary Movie 3

This video is constructed from T2 sagittal images of patient NG 190-1 (photographically inverted) and it shows diffuse cortical volume loss and marked craniofacial disproportion (see Supplementary Information file for full legend). (MOV 3957 kb)

Supplementary Movie 4

This video is constructed from T2 coronal images of patient NG 190-1 (photographically inverted) and it shows diffuse cortical volume loss and marked craniofacial disproportion (see Supplementary Information file for full legend). (MOV 3672 kb)

Supplementary Movie 5

This video is constructed from T1 sagittal images (photographically inverted) of patient NG 891-1 and it demonstrates radiographic findings consistent with microlissencephaly including prominent microcephaly (see Supplementary Information file for full legend). (MOV 716 kb)

Supplementary Movie 6

This video is constructed from T1 coronal images (photographically inverted) of patient NG 891-1 and it demonstrates radiographic findings consistent with microlissencephaly including prominent microcephaly (see Supplementary Information file for full legend). (MOV 119 kb)

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Bilgüvar, K., Öztürk, A., Louvi, A. et al. Whole-exome sequencing identifies recessive WDR62 mutations in severe brain malformations.Nature 467, 207–210 (2010). https://doi.org/10.1038/nature09327

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• Received: 11 May 2010
• Accepted: 30 June 2010
• Published: 22 August 2010
• Issue Date: 09 September 2010
• DOI: https://doi.org/10.1038/nature09327