We have shown that disturbed speech, language, and reading development can sometimes be the result of rare mutations that have dramatic effects on gene function. Our early work identified distinct mutations that disrupt the FOXP2 gene and cause childhood apraxia of speech. This is a developmental disorder characterised by difficulties with automatically and accurately sequencing speech sounds into syllables, syllables into words, and words into sentences with correct prosody. However, damage to the FOXP2 gene accounts for only a small proportion of such cases in the population. The advent of cost-effective high-throughput DNA sequencing has given rise to exciting new opportunities to track down mutations in other genes that can lead to severe speech, language, and reading disorders. These advances are enabling us to move beyond FOXP2, to identify and characterise novel risk genes. For example, in our whole genome sequencing study of 19 unrelated children with severe speech apraxia, we uncovered distinct disruptive mutations affecting CHD3, SETD1A, WDR5, SETBP1, and other genes with known links to brain development.
Snijders Blok, L., et al (2019) De novo variants disturbing the transactivation capacity of POU3F3 cause a characteristic neurodevelopmental disorder. The Americain Journal of Human genetics, 105(2), 403-412. doi.org/10.1016/j.ajhg.2019.06.007. [pdf]
Snijders Blok, L. et al. (2018) De novo mutations in MED13, a component of the Mediator complex, are associated with a novel neurodevelopmental disorder. Human Genetics, 137(5), 375-388. doi:10.1007/s00439-018-1887-y. [pdf]
Snijders Blok, L., et al. (2018) CHD3 helicase domain mutations cause a neurodevelopmental syndrome with macrocephaly and impaired speech and language. Nature Communications, 9, 4619. doi:10.1038/s41467-018-06014-6. [pdf]
Eising, E., et al. (2018). A set of regulatory genes co-expressed in the embryonic human brain is implicated in disrupted speech development. Molecular Psychiatry. Advance online publication. doi:10.1038/s41380-018-0020-x. [pdf]