title: Structural brain abnormalities in a single gene disorder associated with epilepsy, language impairment and intellectual disability.
abstract: Childhood speech and language deficits are highly prevalent and are a common feature of neurodevelopmental disorders. However, it is difficult to investigate the underlying causal pathways because many diagnostic groups have a heterogeneous aetiology. Studying disorders with a shared genetic cause and shared cognitive deficits can provide crucial insight into the cellular mechanisms and neural systems that give rise to those impairments. The current study investigated structural brain differences of individuals with mutations inZDHHC9, which is associated with a specific neurodevelopmental phenotype including prominent speech and language impairments and intellectual disability. We used multiple structural neuroimaging methods to characterise neuroanatomy in this group, and observed bilateral reductions in cortical thickness in areas surrounding the temporo-parietal junction, parietal lobule, and inferior frontal lobe, and decreased microstructural integrity of cortical, subcortical-cortical, and interhemispheric white matter projections. These findings are compared to reports for other genetic groups and genetically heterogeneous disorders with a similar presentation. Overlap in the neuroanatomical phenotype suggests a common pathway that particularly affects the development of temporo-parietal and inferior frontal areas, and their connections.
authors.affiliation: MRC Cognition & Brain Sciences Unit, Cambridge, United Kingdom.
authors.forename: Joe
authors.initials: J
authors.lastname: Bathelt
authors.affiliation: MRC Cognition & Brain Sciences Unit, Cambridge, United Kingdom.
authors.forename: Duncan
authors.initials: D
authors.lastname: Astle
authors.affiliation: MRC Cognition & Brain Sciences Unit, Cambridge, United Kingdom.
authors.forename: Jessica
authors.initials: J
authors.lastname: Barnes
authors.affiliation: Department of Medical Genetics, Cambridge Institute for Medical Research, University of Cambridge, Cambridge, United Kingdom.
authors.forename: F Lucy
authors.initials: FL
authors.lastname: Raymond
authors.affiliation: MRC Cognition & Brain Sciences Unit, Cambridge, United Kingdom; Department of Medical Genetics, Cambridge Institute for Medical Research, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Kate
authors.initials: K
authors.lastname: Baker
mesh_terms: D000217:Acyltransferases / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D001921:Brain / Q000000981:diagnostic imaging / Q000473:pathology*; D004827:Epilepsy / Q000000981:diagnostic imaging / Q000235:genetics* / Q000473:pathology*; D006801:Humans; D008607:Intellectual Disability / Q000000981:diagnostic imaging / Q000235:genetics* / Q000473:pathology*; D007805:Language Development Disorders / Q000000981:diagnostic imaging / Q000235:genetics / Q000473:pathology; D007806:Language Disorders / Q000000981:diagnostic imaging / Q000235:genetics* / Q000473:pathology*; D000073658:Loss of Function Mutation; D008279:Magnetic Resonance Imaging; D008297:Male; D009434:Neural Pathways / Q000000981:diagnostic imaging / Q000473:pathology; D066127:White Matter / Q000000981:diagnostic imaging / Q000473:pathology; D055815:Young Adult
chemical_list: D000217:Acyltransferases; C504825:ZDHHC9 protein, human
keywords: Cognitive development; Cortical morphology; Diffusion-weighted imaging; Human genetics; Language