scholarly journals Functional genetic characterization by CRISPR-Cas9 of two enhancers of FOXP2 in a child with speech and language impairment

2016 ◽  
Author(s):  
R. Torres-Ruiz ◽  
A. Benitez-Burraco ◽  
M. Martínez-Lage ◽  
S. Rodríguez-Perales ◽  
P. García-Bellido
Keyword(s):  
Language Impairment ◽  
Cognitive Abilities ◽  
Neuronal Development ◽  
Regulatory Elements ◽  
Coding Region ◽  
Speech And Language ◽  
Protein Levels ◽  
Speech And Language Impairment ◽  
Dna Elements ◽  
Regulatory Dna

ABSTRACTMutations in the coding region of FOXP2 are known to cause speech and language impairment. Microdeletions involving the region downstream the gene have been also associated to speech and cognitive deficits. We recently described a girl harbouring a complex chromosomal rearrangement with one breakpoint downstream the gene that might affect her speech and cognitive abilities via physical separation of distant regulatory DNA elements. In this study, we have used highly efficient targeted chromosomal deletions induced by the CRISPR/Cas9 genome editing tool to demonstrate the functionality of two enhancers, FOXP2-Eproximal and FOXP2-Edistal, located in the intergenic region between FOXP2 and its adjacent MDFIC gene. Deletion of any of these two functional enhancers in the neuroblastomic cell line SK-N-MC downregulates FOXP2 and decreases FOXP2 protein levels, conversely it upregulates MDFIC and increases MDFIC protein levels. This suggests that both regulatory elements may be shared between FOXP2 and MDFIC. We expect these findings contribute to a deeper understanding of how FOXP2 and MDFIC are regulated to pace neuronal development supporting speech and language.

Speech and language impairment and oromotor dyspraxia due to deletion of 7q31 that involvesFOXP2

2006 ◽  
Vol 140A (5) ◽  
pp. 509-514 ◽  
Author(s):  
Susan Zeesman ◽  
Małgorzata J.M. Nowaczyk ◽  
Ikuko Teshima ◽  
Wendy Roberts ◽  
Janis Oram Cardy ◽  
...  
Keyword(s):  
Language Impairment ◽  
Speech And Language ◽  
Speech And Language Impairment

Pitch and Timing Abilities in Inherited Speech and Language Impairment

2000 ◽  
Vol 75 (1) ◽  
pp. 34-46 ◽  
Author(s):  
Katherine J. Alcock ◽  
Richard E. Passingham ◽  
Kate Watkins ◽  
Faraneh Vargha-Khadem
Keyword(s):  
Language Impairment ◽  
Speech And Language ◽  
Speech And Language Impairment

scholarly journals Population-Based Screening of Children for Specific Speech and Language Impairment in Germany: A Systematic Review

2011 ◽  
Vol 63 (5) ◽  
pp. 247-263 ◽  
Author(s):  
Jürgen Kasper ◽  
Julia Kreis ◽  
Fülöp Scheibler ◽  
Delia Möller ◽  
Guido Skipka ◽  
...  
Keyword(s):  
Systematic Review ◽  
Language Impairment ◽  
Population Based ◽  
Speech And Language ◽  
Speech And Language Impairment

scholarly journals Metabolic and Structural Signatures of Speech and Language Impairment in Corticobasal Syndrome: A Multimodal PET/MRI Study

2021 ◽  
Vol 12 ◽  
Author(s):  
Jacy Bezerra Parmera ◽  
Isabel Junqueira de Almeida ◽  
Marcos Castello Barbosa de Oliveira ◽  
Marcela Lima Silagi ◽  
Camila de Godoi Carneiro ◽  
...  
Keyword(s):  
Language Impairment ◽  
Fdg Pet ◽  
Verbal Fluency ◽  
Inferior Frontal Gyrus ◽  
Premotor Cortex ◽  
Corticobasal Syndrome ◽  
Speech And Language ◽  
Positive Correlation ◽  
Major Cluster ◽  
Speech And Language Impairment

Introduction: Corticobasal syndrome (CBS) is a progressive neurological disorder related to multiple underlying pathologies, including four-repeat tauopathies, such as corticobasal degeneration and progressive supranuclear palsy, and Alzheimer's disease (AD). Speech and language are commonly impaired, encompassing a broad spectrum of deficits. We aimed to investigate CBS speech and language impairment patterns in light of a multimodal imaging approach.Materials and Methods: Thirty-one patients with probable CBS were prospectively evaluated concerning their speech–language, cognitive, and motor profiles. They underwent positron emission tomography with [18F]fluorodeoxyglucose (FDG-PET) and [11C]Pittsburgh Compound-B (PIB-PET) on a hybrid PET-MRI machine to assess their amyloid status. PIB-PET images were classified based on visual and semi-quantitative analyses. Quantitative group analyses were performed on FDG-PET data, and atrophy patterns on MRI were investigated using voxel-based morphometry (VBM). Thirty healthy participants were recruited as imaging controls.Results: Aphasia was the second most prominent cognitive impairment, presented in 67.7% of the cases, following apraxia (96.8%). We identified a wide linguistic profile, ranging from nonfluent variant-primary progressive aphasia to lexical–semantic deficits, mostly with impaired verbal fluency. PIB-PET was classified as negative (CBS-A– group) in 18/31 (58%) and positive (CBS-A+ group) in 13/31 (42%) patients. The frequency of dysarthria was significantly higher in the CBS-A– group than in the CBS-A+ group (55.6 vs. 7.7%, p = 0.008). CBS patients with dysarthria had a left-sided hypometabolism at frontal regions, with a major cluster at the left inferior frontal gyrus and premotor cortex. They showed brain atrophy mainly at the opercular frontal gyrus and putamen. There was a positive correlation between [18F]FDG uptake and semantic verbal fluency at the left inferior (p = 0.006, R2 = 0.2326), middle (0.0054, R2 = 0.2376), and superior temporal gyri (p = 0.0066, R2 = 0.2276). Relative to the phonemic verbal fluency, we found a positive correlation at the left frontal opercular gyrus (p = 0.0003, R2 = 0.3685), the inferior (p = 0.0004, R2 = 0.3537), and the middle temporal gyri (p = 0.0001, R2 = 0.3993).Discussion: In the spectrum of language impairment profile, dysarthria might be helpful to distinguish CBS patients not related to AD. Metabolic and structural signatures depicted from this feature provide further insights into the motor speech production network and are also helpful to differentiate CBS variants.

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