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MAP1B mutations cause intellectual disability and extensive white matter deficit

MAP1B mutations cause intellectual disability and extensive white matter deficit

Title: MAP1B mutations cause intellectual disability and extensive white matter deficit
Author: Walters, G. Bragi   orcid.org/0000-0002-5415-6487
Gústafsson, Ómar
Sveinbjornsson, Gardar   orcid.org/0000-0003-2429-9468
Eiriksdottir, Valgerdur Kristin   orcid.org/0000-0003-0110-1877
Ágústsdóttir, Arna B.
Jónsdóttir, Guðrún A.
Steinberg, Stacy
Gunnarsson, Árni F.
Magnússon, Magnús I.
Unnsteinsdóttir, Unnur
... 18 more authors Show all authors
Date: 2018-08-27
Language: English
Scope: 3456
University/Institute: Háskóli Íslands (HÍ)
University of Iceland (UI)
School: Heilbrigðisvísindasvið (HÍ)
School of Health Sciences (UI)
School of Engineering and Natural Sciences (UI)
Verkfræði- og náttúruvísindasvið (HÍ)
Department: Faculty of Medicine (UI)
Læknadeild (HÍ)
Faculty of Electrical and Computer Engineering (UI)
Rafmagns- og tölvuverkfræðideild (HÍ)
Series: Nature Communications;9(1)
ISSN: 2041-1723
DOI: 10.1038/s41467-018-05595-6
Subject: Developmental disorders; Genetics of the nervous system; Magnetic resonance imaging; Medical genetics; Þroskafrávik; Taugakerfi; Erfðafræði; Læknisfræði
URI: https://hdl.handle.net/20.500.11815/1390

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Walters, G.B., Gustafsson, O., Sveinbjornsson, G. et al. MAP1B mutations cause intellectual disability and extensive white matter deficit. Nat Commun 9, 3456 (2018) doi:10.1038/s41467-018-05595-6


Discovery of coding variants in genes that confer risk of neurodevelopmental disorders is an important step towards understanding the pathophysiology of these disorders. Wholegenome sequencing of 31,463 Icelanders uncovers a frameshift variant (E712KfsTer10) in microtubule-associated protein 1B (MAP1B) that associates with ID/low IQ in a large pedigree (genome-wide corrected P = 0.022). Additional stop-gain variants in MAP1B (E1032Ter and R1664Ter) validate the association with ID and IQ. Carriers have 24% less white matter (WM) volume (β = −2.1SD, P = 5.1 × 10−8), 47% less corpus callosum (CC) volume (β = −2.4SD, P = 5.5 × 10−10) and lower brain-wide fractional anisotropy (P = 6.7 × 10−4). In summary, we show that loss of MAP1B function affects general cognitive ability through a profound, brain-wide WM deficit with likely disordered or compromised axons.


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