Targeted sequencing identifies 91 neurodevelopmental-disorder risk genes with autism and developmental-disability biases

Holly A.F. Stessman; Bo Xiong; Bradley P. Coe; Tianyun Wang; Kendra Hoekzema; Michaela Fenckova; Malin Kvarnung; Jennifer Gerdts; Sandy Trinh; Nele Cosemans; Laura Vives; Janice Lin; Tychele N. Turner; Gijs Santen; Claudia Ruivenkamp; Marjolein Kriek; Arie Van Haeringen; Emmelien Aten; Kathryn Friend; Jan Liebelt; Christopher Barnett; Eric Haan; Marie Shaw; Jozef Gecz; Britt Marie Anderlid; Ann Nordgren; Anna Lindstrand; Charles Schwartz; R. Frank Kooy; Geert Vandeweyer; Celine Helsmoortel; Corrado Romano; Antonino Alberti; Mirella Vinci; Emanuela Avola; Stefania Giusto; Eric Courchesne; Tiziano Pramparo; Karen Pierce; Srinivasa Nalabolu; David G. Amaral; Ingrid E. Scheffer; Martin B. Delatycki; Paul J. Lockhart; Fereydoun Hormozdiari; Benjamin Harich; Anna Castells-Nobau; Kun Xia; Hilde Peeters; Magnus Nordenskjöld; Annette Schenck; Raphael A. Bernier; Evan E. Eichler

doi:10.1038/ng.3792

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Targeted sequencing identifies 91 neurodevelopmental-disorder risk genes with autism and developmental-disability biases

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Targeted sequencing identifies 91 neurodevelopmental-disorder risk genes with autism and developmental-disability biases

Holly A.F. Stessman, Bo Xiong, Bradley P. Coe, Tianyun Wang, Kendra Hoekzema, Michaela Fenckova, Malin Kvarnung, Jennifer Gerdts, Sandy Trinh, Nele Cosemans, …

Nature genetics, Vol.49(4), pp.515-526

03/30/2017

DOI: https://doi.org/10.1038/ng.3792

PMID: 28191889

Abstract

Genetics

Gene-disruptive mutations contribute to the biology of neurodevelopmental disorders (NDDs), but most of the related pathogenic genes are not known. We sequenced 208 candidate genes from >11,730 cases and >2,867 controls. We identified 91 genes, including 38 new NDD genes, with an excess of de novo mutations or private disruptive mutations in 5.7% of cases. Drosophila functional assays revealed a subset with increased involvement in NDDs. We identified 25 genes showing a bias for autism versus intellectual disability and highlighted a network associated with high-functioning autism (full-scale IQ >100). Clinical follow-up for NAA15, KMT5B, and ASH1L highlighted new syndromic and nonsyndromic forms of disease.

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Title: Targeted sequencing identifies 91 neurodevelopmental-disorder risk genes with autism and developmental-disability biases
Creators: Holly A.F. Stessman (Author) - Department of Pharmacology and Neuroscience
Bo Xiong (Author) - University of Washington;Creighton University
Bradley P. Coe (Author) - University of Washington
Tianyun Wang (Author) - Central South University
Kendra Hoekzema (Author) - University of Washington;Huazhong University of Science and Technology
Michaela Fenckova (Author) - Radboud University Nijmegen
Malin Kvarnung (Author) - Karolinska Institutet
Jennifer Gerdts (Author) - University of Washington
Sandy Trinh (Author) - University of Washington
Nele Cosemans (Author) - KU Leuven
Laura Vives (Author) - University of Washington
Janice Lin (Author) - University of Washington
Tychele N. Turner (Author) - University of Washington
Gijs Santen (Author) - Leiden University
Claudia Ruivenkamp (Author) - Leiden University
Marjolein Kriek (Author) - Leiden University
Arie Van Haeringen (Author) - Leiden University
Emmelien Aten (Author) - Leiden University
Kathryn Friend (Author) - University of Adelaide;Genetics and Molecular Pathology
Jan Liebelt (Author) - Women's and Children's Hospital Adelaide
Christopher Barnett (Author) - Women's and Children's Hospital Adelaide
Eric Haan (Author) - University of Adelaide;Women's and Children's Hospital Adelaide
Marie Shaw (Author) - University of Adelaide
Jozef Gecz (Author) - University of Adelaide;Genetics and Molecular Pathology;South Australian Health And Medical Research Institute
Britt Marie Anderlid (Author) - Karolinska Institutet
Ann Nordgren (Author) - Karolinska Institutet
Anna Lindstrand (Author) - Karolinska Institutet
Charles Schwartz (Author) - Greenwood Genetics Center
R. Frank Kooy (Author) - University of Antwerp
Geert Vandeweyer (Author) - University of Antwerp
Celine Helsmoortel (Author) - University of Antwerp
Corrado Romano (Author) - IRCCS Oasi Maria SS. - Troina (EN)
Antonino Alberti (Author) - IRCCS Oasi Maria SS. - Troina (EN)
Mirella Vinci (Author) - IRCCS Oasi Maria SS. - Troina (EN)
Emanuela Avola (Author) - IRCCS Oasi Maria SS. - Troina (EN)
Stefania Giusto (Author) - IRCCS Oasi Maria SS. - Troina (EN)
Eric Courchesne (Author) - University of California at San Diego
Tiziano Pramparo (Author) - University of California at San Diego
Karen Pierce (Author) - University of California at San Diego
Srinivasa Nalabolu (Author) - University of California at San Diego
David G. Amaral (Author) - University of California at Davis
Ingrid E. Scheffer (Author) - University of Melbourne;Florey Institute of Neuroscience and Mental Health
Martin B. Delatycki (Author) - University of Melbourne;Victorian Clinical Genetics Services;Murdoch Children's Research Institute
Paul J. Lockhart (Author) - University of Melbourne;Murdoch Children's Research Institute
Fereydoun Hormozdiari (Author) - University of California at Davis
Benjamin Harich (Author) - Radboud University Nijmegen
Anna Castells-Nobau (Author) - Radboud University Nijmegen
Kun Xia (Author) - Central South University
Hilde Peeters (Author) - KU Leuven
Magnus Nordenskjöld (Author) - Karolinska Institutet
Annette Schenck (Author) - Radboud University Nijmegen
Raphael A. Bernier (Author) - University of Washington
Evan E. Eichler (Author) - University of Washington;Howard Hughes Medical Institute
Publication Details: Nature genetics, Vol.49(4), pp.515-526
Series: 49
Number of pages: 12
Identifiers: 991005930845202656
Academic Unit: Pharmacology and Neuroscience
Language: English
Resource Type: Journal article

Targeted sequencing identifies 91 neurodevelopmental-disorder risk genes with autism and developmental-disability biases

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