MAP1B mutations cause intellectual disability and extensive white matter deficit.

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