A set of regulatory genes co-expressed in embryonic human brain is implicated in disrupted speech development

• DOI: 10.1038/s41380-018-0020-x
• Publication Date: 2018-02-20T20:43:37Z
• Authors: Else Eising; Amaia Carrion-Cas...; Arianna Vino; Edythe A. Strand; Kathy J. Jakielski; Thomas S. Scerri; Michael S. Hildeb...; Richard Webster; Alan Ma; Bernard Mazoyer; Clyde Francks; Melanie Bahlo; Ingrid E. Scheffer; Angela T. Morgan; Lawrence D. Shriberg; Simon E. Fisher
• Keywords: FOXP2; Proband

Genetic investigations of people with impaired development spoken language provide windows into key aspects human biology. Over 15 years after FOXP2 was identified, most speech and impairments remain unexplained at the molecular level. We sequenced whole genomes nineteen unrelated individuals diagnosed childhood apraxia speech, a rare disorder enriched for causative mutations large effect. Where DNA available from unaffected parents, we discovered de novo mutations, implicating genes, including CHD3, SETD1A WDR5. In other probands, identified novel loss-of-function variants affecting KAT6A, SETBP1, ZFHX4, TNRC6B MKL2, regulatory genes links to neurodevelopment. Several new candidates interact each or known speech-related genes. Moreover, they show significant clustering within single co-expression module highly expressed during early brain development. This study highlights gene pathways in developing that may contribute acquisition proficient speech.