Genetic aetiologies for childhood speech disorder: novel pathways co-expressed during brain development

A Kaspi; MS Hildebrand; VE Jackson; R Braden; O van Reyk; T Howell; S Debono; M Lauretta; L Morison; MJ Coleman; R Webster; D Coman; H Goel; M Wallis; G Dabscheck; L Downie; EK Baker; B Parry-Fielder; K Ballard; E Harrold; S Ziegenfusz; MF Bennett; E Robertson; L Wang; A Boys; SE Fisher; DJ Amor; IE Scheffer; M Bahlo; AT Morgan

Journal article

Genetic aetiologies for childhood speech disorder: novel pathways co-expressed during brain development

A Kaspi, MS Hildebrand, VE Jackson, R Braden, O van Reyk, T Howell, S Debono, M Lauretta, L Morison, MJ Coleman, R Webster, D Coman, H Goel, M Wallis, G Dabscheck, L Downie, EK Baker, B Parry-Fielder, K Ballard, E Harrold Show all

Molecular Psychiatry | SPRINGERNATURE | Published : 2023

DOI: 10.1038/s41380-022-01764-8

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Abstract

Childhood apraxia of speech (CAS), the prototypic severe childhood speech disorder, is characterized by motor programming and planning deficits. Genetic factors make substantive contributions to CAS aetiology, with a monogenic pathogenic variant identified in a third of cases, implicating around 20 single genes to date. Here we aimed to identify molecular causation in 70 unrelated probands ascertained with CAS. We performed trio genome sequencing. Our bioinformatic analysis examined single nucleotide, indel, copy number, structural and short tandem repeat variants. We prioritised appropriate variants arising de novo or inherited that were expected to be damaging based on in silico prediction..

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University of Melbourne Researchers

Michael Hildebrand Author

Vicki Jackson Author

Ruth Braden Author

Mariana Lauretta Author

Related Projects (1)

CENTRE FOR RESEARCH EXCELLENCE IN SPEECH AND LANGUAGE NEUROBIOLOGY (CRE-SLANG)

Half a million Australian children have a speech/language disorder, tripling their changes of poor academic outcomes, limited employment opt..

Grants

Awarded by Max-Planck-Gesellschaft

Funding Acknowledgements

This work was funded by a National Health and Medical Research Council (NHMRC) Centre of Research Excellence Grant (CRE-SLANG; 1116976, AM, MH, IS, MB, DA, SEF) and an NHMRC project grant (1160893, AM, MB, DA, MH, SEF). AM was supported by an NHMRC Practitioner Fellowship (1105008) and Investigator grant (1195955). KB was supported by Australian Research Council Future Fellowship (120100355). MB was supported by a NHMRC Senior Research Fellowship (1102971) and a NHMRC Investigator grant (1195236). IS was supported by an NHMRC Investigator grant (1172897). SEF is supported by the Max Planck Society. Additional funding was provided by the Independent Research Institute Infrastructure Support Scheme and the Victorian State Government Operational Infrastructure Program. Open Access funding enabled and organized by CAUL and its Member Institutions.