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

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

doi:10.1038/s41380-018-0020-x

Cited by 122 publications

(148 citation statements)

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“…The discovery that variants of FOXP2 were associated with a rare and monogenic form of CAS catalysed the study of further genes for speech and language disorders. More than 15 years after the FOXP2 discovery, microarray and next‐generation technologies now enable rapid and relatively cost‐efficient genetic testing and have led to a proliferation of further discoveries of gene pathways associated with CAS …”

Section: Genetic Bases Of Casmentioning

confidence: 99%

“…It was beyond the scope of this article to provide an exhaustive summary of all neurogenetic syndromes, copy number‐variant conditions or even chromosomal rearrangements associated with CAS; however, CAS has been associated with conditions such as Floating‐Harbor syndrome, Cri du chat syndrome, galactosaemia, 6q25.3 deletion, 7q11.23 duplication and chromosomal translocations . Moreover, we have not covered recently identified genes for CAS, where replication or further evidence of the relevance of these candidates to the broader population of CAS is not yet clear …”

Section: Genetic Bases Of Casmentioning

confidence: 99%

“…Yet recent reports of germline chromosomal deletions and truncating mutations in SETBP1 show that loss‐of‐function mutations cause a markedly different and less severe phenotype, with impaired expressive speech, relatively intact receptive language abilities, decreased fine motor skills, hyperactivity/ADHD, autistic traits and subtle dysmorphism . Most recently, the phenotype was expanded to specify two cases with CAS with a SETBP1 frameshift mutation and de novo LoF mutation, respectively …”

Section: Genetic Bases Of Casmentioning

confidence: 99%

“…More than 15 years after the FOXP2 discovery, microarray and next-generation technologies now enable rapid and relatively cost-efficient genetic testing and have led to a proliferation of further discoveries of gene pathways associated with CAS. [13][14][15][16]25,26 To highlight the rapidly growing aetiological knowledge in this field, and the presence of significant neurodevelopmental comorbidity for many cases with CAS, we will illustrate genotypephenotype associations for a handful of single-gene variant and copy number-variant conditions associated with CAS ( Table 2). It was beyond the scope of this article to provide an exhaustive summary of all neurogenetic syndromes, copy number-variant conditions or even chromosomal rearrangements associated with CAS; however, CAS has been associated with conditions such as Floating-Harbor syndrome, 27 Cri du chat syndrome, 28 galactosaemia, 29 6q25.3 deletion, 16 7q11.23 duplication 26 and chromosomal translocations.…”

Section: Genetic Bases Of Casmentioning

confidence: 99%

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Aetiology of childhood apraxia of speech: A clinical practice update for paediatricians

Morgan

Webster

2018

J Paediatrics Child Health

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Childhood apraxia of speech (CAS) is a rare disorder of childhood that can leave a watermark of the impacts throughout the lifetime. Since being first described in the 1950s, aetiological insights have been limited. At a neurobiological level, clinical MRI scans fail to reveal overt neural anomalies in individual cases with CAS, although quantitative MRI methods have revealed subtle brain anomalies at a group level. Dramatic insights, however, occurred in the past decade from the discovery of genetic pathways underlying the phenotype. Several single genes and copy number‐variant conditions are now associated with CAS either in relative isolation, as in the case of FOXP2 variants, or most typically in association with other neurodevelopmental conditions, such as epilepsy, intellectual disability, motor impairment and autism. CAS requires careful differential diagnosis from other childhood speech disorders, but when a severe and persistent diagnosis is confirmed, a genetic aetiology should increasingly be pursued.

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Section: Genetic Bases Of Casmentioning

confidence: 99%

Section: Genetic Bases Of Casmentioning

confidence: 99%

Section: Genetic Bases Of Casmentioning

confidence: 99%

Section: Genetic Bases Of Casmentioning

confidence: 99%

See 2 more Smart Citations

Aetiology of childhood apraxia of speech: A clinical practice update for paediatricians

Morgan

Webster

2018

J Paediatrics Child Health

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“…Although rare in the disorder, LoF mutations in SETD1A are substantially depleted in people without a neuropsychiatric diagnosis, identified in only 2 of 45,376 such individuals (compared to a frequency of 0.13% in schizophrenia cases) in the study of Singh et al [3]. Furthermore, rare, heterozygous LoF mutations in SETD1A have been found in individuals diagnosed as having developmental disorders and childhood apraxia of speech [3, 4]. …”

Section: Introductionmentioning

confidence: 99%

Transcriptional Changes following Cellular Knockdown of the Schizophrenia Risk Gene <b><i>SETD1A</i></b> Are Enriched for Common Variant Association with the Disorder

et al. 2019

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Loss of function mutations in SETD1A are the first experiment-wide significant findings to emerge from exome sequencing studies of schizophrenia. Although SETD1Ais known to encode a histone methyltransferase, the consequences of reduced SETD1A activity on gene expression in neural cells have, to date, been unknown. To explore transcriptional changes through which genetic perturbation of SETD1A could confer risk for schizophrenia, we have performed genome-wide gene expression profiling of a commonly used human neuroblastoma cell line in which SETD1A expression has been experimentally reduced using RNA interference (RNAi). We identified 1,031 gene expression changes that were significant in two separate RNAi conditions compared with control, including effects on genes of known neurodevelopmental importance such as DCX and DLX5. Genes that were differentially expressed following SETD1A knockdown were enriched for annotation to metabolic pathways, peptidase regulator activity and integrin-mediated regulation of cell adhesion. Moreover, differentially expressed genes were enriched for common variant association with schizophrenia, suggesting a degree of molecular convergence between this rare schizophrenia risk factor and susceptibility variants for the disorder operating more generally.

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Interventions for childhood apraxia of speech

Morgan

Murray

Liégeois

2018

Cochrane Database of Systematic Reviews

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Background Childhood apraxia of speech (CAS) affects a child's ability to produce sounds and syllables precisely and consistently, and to produce words and sentences with accuracy and correct speech rhythm. It is a rare condition, affecting only 0.1% of the general population. Consensus has been reached that three core features have diagnostic validity: (1) inconsistent error production on both consonants and vowels across repeated productions of syllables or words; (2) lengthened and impaired coarticulatory transitions between sounds and syllables; and (3) inappropriate prosody (ASHA 2007). A deficit in motor programming or planning is thought to underlie the condition. This means that children know what they would like to say but there is a breakdown in the ability to programme or plan the fine and rapid movements required to accurately produce speech. Children with CAS may also have impairments in one or more of the following areas: non-speech oral motor function, dysarthria, language, phonological production impairment, phonemic awareness or metalinguistic skills and literacy, or combinations of these. High-quality evidence from randomised controlled trials (RCTs) is lacking on interventions for CAS. Objectives To assess the efficacy of interventions targeting speech and language in children and adolescents with CAS as delivered by speech and language pathologists/therapists. Search methods We searched CENTRAL, MEDLINE, Embase, eight other databases and seven trial registers up to April 2017. We searched the reference lists of included reports and requested information on unpublished trials from authors of published studies and other experts as well as information groups in the areas of speech and language therapy/pathology and linguistics. Selection criteria RCTs and quasi-RCTs of children aged 3 to 16 years with CAS diagnosed by a speech and language pathologist/therapist, grouped by treatment types. Data collection and analysis Two review authors (FL, AM) independently assessed titles and abstracts identified from the searches and obtained full-text reports of all potentially relevant articles and assessed these for eligibility. The same two authors extracted data and conducted the 'Risk of bias' and GRADE assessments. One review author (EM) tabulated findings from excluded observational studies (Table 1). 1 Interventions for childhood apraxia of speech (Review)

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

Cited by 122 publications

References 68 publications

Aetiology of childhood apraxia of speech: A clinical practice update for paediatricians

Aetiology of childhood apraxia of speech: A clinical practice update for paediatricians

Transcriptional Changes following Cellular Knockdown of the Schizophrenia Risk Gene <b><i>SETD1A</i></b> Are Enriched for Common Variant Association with the Disorder

Interventions for childhood apraxia of speech

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