Journal article

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

Else Eising, Amaia Carrion-Castillo, Arianna Vino, Edythe A Strand, Kathy J Jakielski, Thomas S Scerri, Michael S Hildebrand, Richard Webster, Alan Ma, Bernard Mazoyer, Clyde Francks, Melanie Bahlo, Ingrid E Scheffer, Angela T Morgan, Lawrence D Shriberg, Simon E Fisher

MOLECULAR PSYCHIATRY | NATURE PUBLISHING GROUP | Published : 2019

Abstract

Genetic investigations of people with impaired development of spoken language provide windows into key aspects of human biology. Over 15 years after FOXP2 was identified, most speech and language impairments remain unexplained at the molecular level. We sequenced whole genomes of nineteen unrelated individuals diagnosed with childhood apraxia of speech, a rare disorder enriched for causative mutations of large effect. Where DNA was available from unaffected parents, we discovered de novo mutations, implicating genes, including CHD3, SETD1A and WDR5. In other probands, we identified novel loss-of-function variants affecting KAT6A, SETBP1, ZFHX4, TNRC6B and MKL2, regulatory genes with links to..

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Grants

Awarded by National Institute on Deafness and Other Communication Disorders Grant


Awarded by National Institute of Child Health and Development


Awarded by National Health and Medical Research Council (NHMRC) Centre of Research Excellence in Speech and Language Neurobiology


Awarded by NHMRC


Awarded by NATIONAL INSTITUTE ON DEAFNESS AND OTHER COMMUNICATION DISORDERS


Funding Acknowledgements

We are grateful to Sarah Graham for assistance with handling of DNA samples and to Heather Mabie for assistance with the phenotype materials. EE, AC-C, AV and SEF were supported by the Max Planck Society. LDS was supported by a National Institute on Deafness and Other Communication Disorders Grant (DC000496) and a core grant to the Waisman Center from the National Institute of Child Health and Development (Grant HD03352). ATM, MSH, IES, MB and SEF are supported by a National Health and Medical Research Council (NHMRC) Centre of Research Excellence in Speech and Language Neurobiology (ID: 1116976). ATM, MSH and SEF are supported by an NHMRC Project grant (1127144). ATM, MSH, IES, and MB are supported by the March of Dimes, United States. ATM was supported by an NHMRC Practitioner Fellowship (1105008). MB was supported by an NHMRC Program Grant (1054618) and NHMRC Senior Research Fellowship (1102971). IES is supported by an NHMRC Program Grant (1091593) and NHMRC Practitioner Fellowship (1006110). This work was supported by the Victorian Government's Operational Infrastructure Support Program and Australian Government NHMRC Independent Research Institute Infrastructure Support Scheme (IRIISS).