A set of regulatory genes co-expressed in embryonic human brain is implicated in disrupted speech development
Mol Psychiatry. 2018-02-20; :
DOI: 10.1038/s41380-018-0020-x
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A set of regulatory genes co-expressed in embryonic human brain is implicated in
disrupted speech development.
Eising E(1), Carrion-Castillo A(1), Vino A(1), Strand EA(2), Jakielski KJ(3),
Scerri TS(4)(5), Hildebrand MS(6), Webster R(7), Ma A(8), Mazoyer B(9), Francks
C(1)(10), Bahlo M(4)(5), Scheffer IE(6)(11), Morgan AT(6)(12), Shriberg LD(13),
Fisher SE(14)(15).
Author information:
(1)Language and Genetics Department, Max Planck Institute for Psycholinguistics,
Nijmegen, 6525 XD, The Netherlands.
(2)Department of Neurology, Mayo Clinic, Rochester, MN, 55905, USA.
(3)Department of Communication Sciences and Disorders, Augustana College, Rock
Island, IL, 61201, USA.
(4)Population Health and Immunity Division, Walter and Eliza Hall Institute of
Medical Research, Melbourne, 3052, Australia.
(5)Department of Medical Biology, University of Melbourne, Melbourne, 3010,
Australia.
(6)Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne,
Melbourne, 3010, Australia.
(7)Department of Neurology and Neurosurgery, Children’s Hospital Westmead,
Sydney, NSW, Australia.
(8)Department of Clinical Genetics, Children’s Hospital Westmead, Sydney, NSW,
Australia.
(9)University of Bordeaux, IMN, UMR 5293, Bordeaux, France.
(10)Donders Institute for Brain, Cognition and Behaviour, Radboud University,
Nijmegen, 6500 HE, The Netherlands.
(11)Austin Health and Royal Children’s Hospital, Melbourne, 3052, Australia.
(12)Neuroscience of Speech, Murdoch Childrens Research Institute, Melbourne,
3052, Australia.
(13)Waisman Center, University of Wisconsin-Madison, Madison, WI, 53705, USA.
(14)Language and Genetics Department, Max Planck Institute for Psycholinguistics,
Nijmegen, 6525 XD, The Netherlands. .
(15)Donders Institute for Brain, Cognition and Behaviour, Radboud University,
Nijmegen, 6500 HE, The Netherlands. .
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
neurodevelopment. Several of the new candidates interact with each other or with
known speech-related genes. Moreover, they show significant clustering within a
single co-expression module of genes highly expressed during early human brain
development. This study highlights gene regulatory pathways in the developing
brain that may contribute to acquisition of proficient speech.
DOI: 10.1038/s41380-018-0020-x
PMID: 29463886