Disruptive mutations in TANC2 define a neurodevelopmental syndrome associated with psychiatric disorders
Hui Guo
(1)
,
Elisa Bettella
(2)
,
Paul Marcogliese
(3, 4)
,
Rongjuan Zhao
(5)
,
Jonathan Andrews
(3, 4)
,
Tomasz Nowakowski
(6)
,
Madelyn Gillentine
(7)
,
Kendra Hoekzema
(8, 7)
,
Tianyun Wang
(7, 5)
,
Huidan Wu
(5)
,
Sharayu Jangam
(3, 4)
,
Cenying Liu
(5)
,
Hailun Ni
(5)
,
Marjolein Willemsen
(9, 10)
,
Bregje van Bon
(9)
,
Tuula Rinne
(9)
,
Servi Stevens
(10)
,
Tjitske Kleefstra
(9)
,
Han Brunner
(9, 10)
,
Helger Yntema
(9)
,
Min Long
(11, 5)
,
Wenjing Zhao
(5)
,
Zhengmao Hu
(5)
,
Cindy Colson
(12, 13)
,
Nicolas Richard
(13, 12)
,
Charles Schwartz
(14)
,
Corrado Romano
(15)
,
Lucia Castiglia
(16)
,
Maria Bottitta
(16)
,
Shweta Dhar
(3)
,
Deanna Erwin
(3)
,
Lisa Emrick
(3)
,
Boris Keren
(17)
,
Alexandra Afenjar
(18)
,
Baosheng Zhu
(19)
,
Bing Bai
(19)
,
Pawel Stankiewicz
(3)
,
Kristin Herman
(6)
,
Saadet Mercimek-Andrews
(20, 21)
,
Jane Juusola
(22)
,
Amy Wilfert
(7)
,
Rami Abou Jamra
(23)
,
Benjamin Büttner
(23)
,
Heather Mefford
(24)
,
Alison Muir
(24)
,
Ingrid E. Scheffer
(25)
,
Brigid Regan
(25)
,
Stephen Malone
(26)
,
Jozef Gecz
(27)
,
Jan Cobben
(28)
,
Marjan Weiss
(29)
,
Quinten Waisfisz
(29)
,
Emilia Bijlsma
(30)
,
Mariëtte Hoffer
(30)
,
Claudia Ruivenkamp
(30)
,
Stefano Sartori
(2)
,
Fan Xia
(3)
,
Jill Rosenfeld
(3)
,
Raphael Bernier
(24)
,
Michael Wangler
(3, 4)
,
Shinya Yamamoto
(3, 4)
,
Kun Xia
(31, 5)
,
Alexander Stegmann
(10, 9)
,
Hugo Bellen
(3, 4)
,
Alessandra Murgia
(2)
,
Evan Eichler
(24)
1
Chinese Academy of Forestry
2 AOUP - Azienda Ospedale Università di Padova = Hospital-University of Padua
3 BCM - Baylor College of Medicine
4 Texas Children's Hospital [Houston, USA]
5 Central South University [Changsha]
6 UC - University of California
7 Washington University School of Medicine in St. Louis
8 GS - Department of Genome Sciences [Seattle]
9 Radboud University Medical Center [Nijmegen]
10 MUMC - Maastricht University Medical Centre
11 UR EMAX - Ecosystèmes méditerranéens et risques
12 Service de Génétique [CHU Caen]
13 BIOTARGEN - Biologie, génétique et thérapies ostéoarticulaires et respiratoires
14 The Greenwood Genetic Center
15 IRCCS - Istituto di Ricovero e Cura a Carattere Scientifico
16 IRCCS - Istituto di Ricovero e Cura a Carattere Scientifico
17 CRICM - Centre de Recherche de l'Institut du Cerveau et de la Moelle épinière
18 CHU Trousseau [APHP]
19 KMUST - Kunming University of Science and Technology
20 SickKids - The Hospital for sick children [Toronto]
21 University of Toronto
22 GeneDx [Gaithersburg, MD, USA]
23 Leipzig University / Universität Leipzig
24 University of Washington [Seattle]
25 University of Melbourne
26 Queensland Institute of Medical Research
27 University of Adelaide
28 Emma Children’s Hospital
29 VU - Vrije Universiteit Amsterdam [Amsterdam]
30 LUMC - Leiden University Medical Center
31 CUHK - The Chinese University of Hong Kong [Hong Kong]
2 AOUP - Azienda Ospedale Università di Padova = Hospital-University of Padua
3 BCM - Baylor College of Medicine
4 Texas Children's Hospital [Houston, USA]
5 Central South University [Changsha]
6 UC - University of California
7 Washington University School of Medicine in St. Louis
8 GS - Department of Genome Sciences [Seattle]
9 Radboud University Medical Center [Nijmegen]
10 MUMC - Maastricht University Medical Centre
11 UR EMAX - Ecosystèmes méditerranéens et risques
12 Service de Génétique [CHU Caen]
13 BIOTARGEN - Biologie, génétique et thérapies ostéoarticulaires et respiratoires
14 The Greenwood Genetic Center
15 IRCCS - Istituto di Ricovero e Cura a Carattere Scientifico
16 IRCCS - Istituto di Ricovero e Cura a Carattere Scientifico
17 CRICM - Centre de Recherche de l'Institut du Cerveau et de la Moelle épinière
18 CHU Trousseau [APHP]
19 KMUST - Kunming University of Science and Technology
20 SickKids - The Hospital for sick children [Toronto]
21 University of Toronto
22 GeneDx [Gaithersburg, MD, USA]
23 Leipzig University / Universität Leipzig
24 University of Washington [Seattle]
25 University of Melbourne
26 Queensland Institute of Medical Research
27 University of Adelaide
28 Emma Children’s Hospital
29 VU - Vrije Universiteit Amsterdam [Amsterdam]
30 LUMC - Leiden University Medical Center
31 CUHK - The Chinese University of Hong Kong [Hong Kong]
Jonathan Andrews
- Fonction : Auteur
- PersonId : 893392
Sharayu Jangam
- Fonction : Auteur
Marjolein Willemsen
- Fonction : Auteur
- PersonId : 906056
Min Long
- Fonction : Auteur
Nicolas Richard
- Fonction : Auteur
- PersonId : 176918
- IdHAL : nicolasrichard
- ORCID : 0000-0003-0702-7399
- IdRef : 178137480
Boris Keren
- Fonction : Auteur
- PersonId : 764775
- ORCID : 0000-0001-6172-8247
Marjan Weiss
- Fonction : Auteur
- PersonId : 797801
- ORCID : 0000-0002-0936-1406
Alexander Stegmann
- Fonction : Auteur
- PersonId : 907008
Résumé
Postsynaptic density (PSD) proteins have been implicated in the pathophysiology of neuro-developmental and psychiatric disorders. Here, we present detailed clinical and genetic data for 20 patients with likely gene-disrupting mutations in TANC2-whose protein product interacts with multiple PSD proteins. Pediatric patients with disruptive mutations present with autism, intellectual disability, and delayed language and motor development. In addition to a variable degree of epilepsy and facial dysmorphism, we observe a pattern of more complex psychiatric dysfunction or behavioral problems in adult probands or carrier parents. Although this observation requires replication to establish statistical significance, it also suggests that mutations in this gene are associated with a variety of neuropsychiatric disorders consistent with its postsynaptic function. We find that TANC2 is expressed broadly in the human developing brain, especially in excitatory neurons and glial cells, but shows a more restricted pattern in Drosophila glial cells where its disruption affects behavioral outcomes.
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