7,766 research outputs found
Increased prevalence of sex chromosome aneuploidies in specific language impairment and dyslexia
No full text© 2013 Mac Keith Press.Sex chromosome aneuploidies increase the risk of spoken or written language disorders but individuals with specific language impairment (SLI) or dyslexia do not routinely undergo cytogenetic analysis. We assess the frequency of sex chromosome aneuploidies in individuals with language impairment or dyslexia.Peer reviewe
Investigating grammatical complexity in Gulf Arabic speaking children with specific language impairment (SLI)
No full textThis is the first investigation of Specific Language Impairment (SLI) in Gulf-Arabic (GA) speaking children. The thesis consists of two main sections, in the first one, I discuss the definitions of SLI and the various theories put forward to account for the deficits seen in this population. I also discuss the importance of cross-linguistic investigations of SLI and why studying SLI in GA may prove useful in testing the accounts of SLI that argue for a general processing deficit vs. those that argue for a domain specific account of SLI. The remaining section of the first part is dedicated to describing the various language tests developed to identify children with SLI in GA. These tests were conducted with approximately 88 typically developing children and 26 children with SLI between the age of 4;6 and 9;4 years old. In the second part of the thesis, I report on two experiments investigating syntactic and phonological complexity in GA speaking children with SLI. The first experiment investigates the comprehension of three types of word orders: a canonical SVO, and two word orders that involve fronting of the direct object (OSV and OVS). Results showed that children with SLI differed from the TD groups on the sentences with fronted NP's, but not on the canonical word order. The second experiment involves a nonword repetition test where syllable length and consonant clusters are systematically controlled to contrast the influence of both phonological short-term memory and phonological complexity. The results are consistent with accounts that argue for a significant role of phonological complexity in NWR and question the “centrality” of phonological capacity in nonword repetition. The final chapter summarises the findings of the thesis and its contribution to theories of SLI in general, and to the study of SLI in Arabic in particular
A genomewide scan identifies two novel loci involved in specific language impairment.
No full textApproximately 4% of English-speaking children are affected by specific language impairment (SLI), a disorder in the development of language skills despite adequate opportunity and normal intelligence. Several studies have indicated the importance of genetic factors in SLI; a positive family history confers an increased risk of development, and concordance in monozygotic twins consistently exceeds that in dizygotic twins. However, like many behavioral traits, SLI is assumed to be genetically complex, with several loci contributing to the overall risk. We have compiled 98 families drawn from epidemiological and clinical populations, all with probands whose standard language scores fall > or =1.5 SD below the mean for their age. Systematic genomewide quantitative-trait-locus analysis of three language-related measures (i.e., the Clinical Evaluation of Language Fundamentals-Revised [CELF-R] receptive and expressive scales and the nonword repetition [NWR] test) yielded two regions, one on chromosome 16 and one on 19, that both had maximum LOD scores of 3.55. Simulations suggest that, of these two multipoint results, the NWR linkage to chromosome 16q is the most significant, with empirical P values reaching 10(-5), under both Haseman-Elston (HE) analysis (LOD score 3.55; P=.00003) and variance-components (VC) analysis (LOD score 2.57; P=.00008). Single-point analyses provided further support for involvement of this locus, with three markers, under the peak of linkage, yielding LOD scores >1.9. The 19q locus was linked to the CELF-R expressive-language score and exceeds the threshold for suggestive linkage under all types of analysis performed-multipoint HE analysis (LOD score 3.55; empirical P=.00004) and VC (LOD score 2.84; empirical P=.00027) and single-point HE analysis (LOD score 2.49) and VC (LOD score 2.22). Furthermore, both the clinical and epidemiological samples showed independent evidence of linkage on both chromosome 16q and chromosome 19q, indicating that these may represent universally important loci in SLI and, thus, general risk factors for language impairment
Associations of HLA alleles with specific language impairment
No full textHuman leukocyte antigen (HLA) loci have been implicated in several neurodevelopmental disorders in which language is affected. However, to date, no studies have investigated the possible involvement of HLA loci in specific language impairment (SLI), a disorder that is defined primarily upon unexpected language impairment. We report association analyses of single-nucleotide polymorphisms (SNPs) and HLA types in a cohort of individuals affected by language impairment. We perform quantitative association analyses of three linguistic measures and case-control association analyses using both SNP data and imputed HLA types. Quantitative association analyses of imputed HLA types suggested a role for the HLA-A locus in susceptibility to SLI. HLA-A A1 was associated with a measure of short-term memory (P = 0.004) and A3 with expressive language ability (P = 0.006). Parent-of-origin effects were found between HLA-B B8 and HLA-DQA1*0501 and receptive language. These alleles have a negative correlation with receptive language ability when inherited from the mother (P = 0.021, P = 0.034, respectively) but are positively correlated with the same trait when paternally inherited (P = 0.013, P = 0.029, respectively). Finally, case control analyses using imputed HLA types indicated that the DR10 allele of HLA-DRB1 was more frequent in individuals with SLI than population controls (P = 0.004, relative risk = 2.575), as has been reported for individuals with attention deficit hyperactivity disorder (ADHD). These preliminary data provide an intriguing link to those described by previous studies of other neurodevelopmental disorders and suggest a possible role for HLA loci in language disorders
Language in autism and specific language impairment: Where are the links?
No full textIt has been suggested that language impairment in autism is behaviourally, neurobiologically, and etiologically related to specific language impairment (SLI). In this paper, we review evidence at each level and argue that the vast majority of data does not support the view that language impairment in autism can be explained in terms of co-morbid SLI. We make recommendations for how this debate might be resolved and we suggest a shift in research focus. We recommend that researchers concentrate on those aspects of language impairment that predominate in each disorder rather than on those comparatively small areas of potential overlap
Genome-wide association analyses of child genotype effects and parent-of-origin effects in specific language impairment
No full textSpecific language impairment (SLI) is a neurodevelopmental disorder that affects linguistic abilities when development is otherwise normal. We report the results of a genome-wide association study of SLI which included parent-of-origin effects and child genotype effects and used 278 families of language-impaired children. The child genotype effects analysis did not identify significant associations. We found genome-wide significant paternal parent-of-origin effects on chromosome 14q12 (P = 3.74 × 10(-8) ) and suggestive maternal parent-of-origin effects on chromosome 5p13 (P = 1.16 × 10(-7) ). A subsequent targeted association of six single-nucleotide-polymorphisms (SNPs) on chromosome 5 in 313 language-impaired individuals and their mothers from the ALSPAC cohort replicated the maternal effects, albeit in the opposite direction (P = 0.001); as fathers' genotypes were not available in the ALSPAC study, the replication analysis did not include paternal parent-of-origin effects. The paternally-associated SNP on chromosome 14 yields a non-synonymous coding change within the NOP9 gene. This gene encodes an RNA-binding protein that has been reported to be significantly dysregulated in individuals with schizophrenia. The region of maternal association on chromosome 5 falls between the PTGER4 and DAB2 genes, in a region previously implicated in autism and ADHD. The top SNP in this association locus is a potential expression QTL of ARHGEF19 (also called WGEF) on chromosome 1. Members of this protein family have been implicated in intellectual disability. In summary, this study implicates parent-of-origin effects in language impairment, and adds an interesting new dimension to the emerging picture of shared genetic etiology across various neurodevelopmental disorders
Multivariate linkage analysis of specific language impairment (SLI)
No full textSpecific language impairment (SLI) is defined as an inability to develop appropriate language skills without explanatory medical conditions, low intelligence or lack of opportunity. Previously, a genome scan of 98 families affected by SLI was completed by the SLI Consortium, resulting in the identification of two quantitative trait loci (QTL) on chromosomes 16q (SLI1) and 19q (SLI2). This was followed by a replication of both regions in an additional 86 families. Both these studies applied linkage methods to one phenotypic trait at a time. However, investigations have suggested that simultaneous analysis of several traits may offer more power. The current study therefore applied a multivariate variance-components approach to the SLI Consortium dataset using additional phenotypic data. A multivariate genome scan was completed and supported the importance of the SLI1 and SLI2 loci, whilst highlighting a possible novel QTL on chromosome 10. Further investigation implied that the effect of SLI1 on non-word repetition was equally as strong on reading and spelling phenotypes. In contrast, SLI2 appeared to have influences on a selection of expressive and receptive language phenotypes in addition to non-word repetition, but did not show linkage to literacy phenotypes
CMIP and ATP2C2 Modulate Phonological Short-Term Memory in Language Impairment
No full textSpecific language impairment (SLI) is a common developmental disorder characterized by difficulties in language acquisition despite otherwise normal development and in the absence of any obvious explanatory factors. We performed a high-density screen of SLI1, a region of chromosome 16q that shows highly significant and consistent linkage to nonword repetition, a measure of phonological short-term memory that is commonly impaired in SLI. Using two independent language-impaired samples, one family-based (211 families) and another selected from a population cohort on the basis of extreme language measures (490 cases), we detected association to two genes in the SLI1 region: that encoding c-maf-inducing protein (CMIP, minP = 5.5 × 10−7 at rs6564903) and that encoding calcium-transporting ATPase, type2C, member2 (ATP2C2, minP = 2.0 × 10−5 at rs11860694). Regression modeling indicated that each of these loci exerts an independent effect upon nonword repetition ability. Despite the consistent findings in language-impaired samples, investigation in a large unselected cohort (n = 3612) did not detect association. We therefore propose that variants in CMIP and ATP2C2 act to modulate phonological short-term memory primarily in the context of language impairment. As such, this investigation supports the hypothesis that some causes of language impairment are distinct from factors that influence normal language variation. This work therefore implicates CMIP and ATP2C2 in the etiology of SLI and provides molecular evidence for the importance of phonological short-term memory in language acquisition
Lack of replication for the myosin-18B association with mathematical ability in independent cohorts
No full textSP is a Royal Society University Research Fellow. This specific study in the ALSPAC cohort was supported by a MRC grant to SP [grant number G0800523/8647]. Support to the analysis was provided by the St Andrews Bioinformatics Unit funded by the Wellcome Trust [grant 097831/Z/11/Z].Twin studies indicate that dyscalculia (or mathematical disability) is caused partly by a genetic component, which is yet to be understood at the molecular level. Recently, a coding variant (rs133885) in the myosin-18B gene was shown to be associated with mathematical abilities with a specific effect among children with dyslexia. This association represents one of the most significant genetic associations reported to date for mathematical abilities and the only one reaching genome-wide statistical significance. We conducted a replication study in different cohorts to assess the effect of rs133885 maths-related measures. The study was conducted primarily using the Avon Longitudinal Study of Parents and Children (ALSPAC), (N = 3819). We tested additional cohorts including the York Cohort, the Specific Language Impairment Consortium (SLIC) cohort and the Raine Cohort, and stratified them for a definition of dyslexia whenever possible. We did not observe any associations between rs133885 in myosin-18B and mathematical abilities among individuals with dyslexia or in the general population. Our results suggest that the myosin-18B variant is unlikely to be a main factor contributing to mathematical abilities.Peer reviewe
Short-term and working memory in children with specific language impairment
No full textInvestigations of the cognitive processes underlying Specific Language Impairment (SLI) have implicated deficits in the storage and processing of phonological or verbal information. This thesis reports five studies that investigated the role of short-term and working memory in children with SLI. Study 1 demonstrated SLI deficits on measures of verbal working memory, and short-term memory for verbal but not visuospatial information. Study 2 provided evidence that children with SLI perform at age-level on visuospatial working memory measures. Study 3 demonstrated slower processing in the SLI group across domains, as well as verbal storage decrements, with the greatest deficits found for tasks tapping both of these. Study 4 found SLI deficits on measures of nonword repetition in common use, with greater impairments on the task that relied to a lesser extent on short-term memory. Study 5 established more accurate recall for multisyllabic nonwords than matched single syllable lists for all groups, although the SLI group showed different patterns of phoneme retention. It is suggested that the combination of deficits in generalized processing speed and verbal storage in SLI may be expected to have a drastic and detrimental impact on learning, and provides an account of the disorder that could encompass the range of impairments observed in SLI. The findings also suggest that factors additional to short-term memory contribute to poor nonword repetition in SLI
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