A set of regulatory genes co-expressed in embryonic human brain is implicated in disrupted speech development.
Apraxias
/ genetics
Brain
/ embryology
Carrier Proteins
/ genetics
DNA Helicases
/ genetics
Gene Expression Regulation, Developmental
/ genetics
Gene Regulatory Networks
/ genetics
Histone Acetyltransferases
/ genetics
Histone-Lysine N-Methyltransferase
/ genetics
Homeodomain Proteins
/ genetics
Humans
Intracellular Signaling Peptides and Proteins
/ genetics
Mi-2 Nucleosome Remodeling and Deacetylase Complex
/ genetics
Nuclear Proteins
/ genetics
RNA-Binding Proteins
/ genetics
Speech
/ physiology
Speech Disorders
/ genetics
Transcription Factors
/ genetics
Journal
Molecular psychiatry
ISSN: 1476-5578
Titre abrégé: Mol Psychiatry
Pays: England
ID NLM: 9607835
Informations de publication
Date de publication:
07 2019
07 2019
Historique:
received:
22
09
2017
accepted:
02
01
2018
revised:
03
12
2017
pubmed:
22
2
2018
medline:
3
3
2020
entrez:
22
2
2018
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 29463886
doi: 10.1038/s41380-018-0020-x
pii: 10.1038/s41380-018-0020-x
pmc: PMC6756287
doi:
Substances chimiques
Carrier Proteins
0
Homeodomain Proteins
0
Intracellular Signaling Peptides and Proteins
0
Nuclear Proteins
0
RNA-Binding Proteins
0
SETBP1 protein, human
0
TNRC6B protein, human
0
Transcription Factors
0
WDR5 protein, human
0
ZFHX4 protein, human
0
Histone-Lysine N-Methyltransferase
EC 2.1.1.43
Setd1A protein, human
EC 2.1.1.43
Histone Acetyltransferases
EC 2.3.1.48
KAT6A protein, human
EC 2.3.1.48
Mi-2 Nucleosome Remodeling and Deacetylase Complex
EC 3.5.1.98
DNA Helicases
EC 3.6.4.-
CHD3 protein, human
EC 3.6.4.12
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1065-1078Subventions
Organisme : NIDCD NIH HHS
ID : R01 DC000496
Pays : United States
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