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Assessing the impact of FOXP1 mutations on developmental verbal dyspraxia.

ABSTRACT: Neurodevelopmental disorders that disturb speech and language are highly heritable. Isolation of the underlying genetic risk factors has been hampered by complexity of the phenotype and potentially large number of contributing genes. One exception is the identification of rare heterozygous mutations of the FOXP2 gene in a monogenic syndrome characterised by impaired sequencing of articulatory gestures, disrupting speech (developmental verbal dyspraxia, DVD), as well as multiple deficits in expressive and receptive language. The protein encoded by FOXP2 belongs to a divergent subgroup of forkhead-box transcription factors, with a distinctive DNA-binding domain and motifs that mediate hetero- and homodimerisation. FOXP1, the most closely related member of this subgroup, can directly interact with FOXP2 and is co-expressed in neural structures relevant to speech and language disorders. Moreover, investigations of songbird orthologues indicate that combinatorial actions of the two proteins may play important roles in vocal learning, leading to the suggestion that human FOXP1 should be considered a strong candidate for involvement in DVD. Thus, in this study, we screened the entire coding region of FOXP1 (exons and flanking intronic sequence) for nucleotide changes in a panel of probands used earlier to detect novel mutations in FOXP2. A non-synonymous coding change was identified in a single proband, yielding a proline-to-alanine change (P215A). However, this was also found in a random control sample. Analyses of non-coding SNP changes did not find any correlation with affection status. We conclude that FOXP1 mutations are unlikely to represent a major cause of DVD.

SUBMITTER: Vernes SC

PROVIDER: S-EPMC2784575 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Children with developmental coordination disorder (DCD) face significant challenges to deal with everyday activities due to underlying motor proficiency difficulties. These challenges affect children and young people's participation; that is, involvement in daily life situations. In the past, limited consideration was given to personal experience of events, relationships and everyday life in children and young people with DCD; as a result, understanding what it is like to live with DCD is not well conceptualised in the literature. There is a pressing need to synthesise the findings of discrete qualitative studies to advance the conceptual understanding of living with DCD, to inform health service delivery and the development and implementation of complex interventions. This study aims to systematically review and synthesise qualitative literature regarding children and young people's experiences and views of everyday life and living with DCD. The method of qualitative evidence synthesis that will be followed in this review is a meta-ethnography. The eMERGe and PRISMA reporting guidelines will be used in the development, design and reporting of this review. Nine databases will be searched; Academic Search Complete, AMED, CINAHL, MEDLINE, PsychArticles, PsychInfo, EMBASE, SPORTDiscus, and Web of Science. Two independent reviewers will use the Joanna Briggs Institute Checklist to appraise all included papers. The findings of this meta-ethnography will endeavour to inform future research, policy and practice. In particular, the results will help to inform the design of future complex interventions to meet the needs of children and young people with DCD. Dissemination will involve the publication of the results in a peer-reviewed journal. Increasingly researchers and policymakers are calling for services to be informed by the perspective and voice of children with DCD; therefore, a policy brief will be published so that the findings are widely available. Registration: PROSPERO registration number CRD42019129178; registered on 09 July 2019.

Project description:BackgroundTo date services for children with Developmental Coordination Disorder (DCD) have not been informed by the perspective of children with DCD. This study aimed to synthesise the findings of discrete qualitative studies reporting the lived experiences views and preferences of children and young with DCD using a meta-ethnographic approach to develop new conceptual understandings.MethodsA systematic search of ten databases; Academic Search Complete, AMED, CINAHL, ERIC, MEDLINE, PsychArticles, PsychInfo, EMBASE, SPORTDiscus, and Web of Science, was conducted between March and April 2019, and updated in early June 2020. Meta-ethnography, following the method described by Noblit and Hare was used to synthesise included studies. The Joanna Briggs Institute Checklist was used to appraise all included papers. PROSPERO registration number CRD42019129178.ResultsFifteen studies met the inclusion criteria. Meta-ethnographic synthesis produced three themes; a) 'It's harder than it should be': Navigating daily activities b) Fitting in, and c) 'So what? I drop things': Strategies and supports to mitigate challenges. Children with DCD describe a mismatch between their abilities and performance norms for daily activities that led to a cascade of negative consequences including negative self-appraisal, bullying and exclusion. In the face of these difficulties children described creative and successful strategies they enacted and supports they accessed including; assistance from others (parents, friends and teachers), focusing on their strengths and talents, accepting and embracing their difference, adopting a "just do it" attitude, setting personal goals, self-exclusion from some social activities, using humour or sarcasm, viewing performance expectations as a social construct, and enjoying friendships as a forum for fun, acceptance and protection against exclusion.ConclusionService provision for children and young people with DCD should address the social and attitudinal environments, focus on friendship and social inclusion and address stigma-based bullying particularly within the school environment. Furthermore, practitioners should identify and foster children's own strategies for navigating daily life activities with DCD. The identified themes resonate with contemporary disability theory and the International Classification of Functioning. The social and attitudinal environmental context of children and young people with DCD profoundly influences their experiences. Future intervention development and service provision for children and young people with DCD should consider opportunities to address social and attitudinal environmental factors.

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Assessing the impact of FOXP1 mutations on developmental verbal dyspraxia.

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