Approximately 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.
The FOXP2 gene, located on human 7q31 (at the SPCH1 locus), encodes a transcription factor containing a polyglutamine tract and a forkhead domain. FOXP2 is mutated in a severe monogenic form of speech and language impairment, segregating within a single large pedigree, and is also disrupted by a translocation in an isolated case. Several studies of autistic disorder have demonstrated linkage to a similar region of 7q (the AUTS1 locus), leading to the proposal that a single genetic factor on 7q31 contributes to both autism and language disorders. In the present study, we directly evaluate the impact of the FOXP2 gene with regard to both complex language impairments and autism, through use of association and mutation screening analyses. We conclude that coding-region variants in FOXP2 do not underlie the AUTS1 linkage and that the gene is unlikely to play a role in autism or more common forms of language impairment.
The Childhood Asperger Syndrome Test (CAST) is a parental questionnaire to screen for autism spectrum conditions. In this validation study, the CAST was distributed to 1925 children aged 5-11 in mainstream Cambridgeshire schools. A sample of participants received a full diagnostic assessment, conducted blind to screen status. The sensitivity of the CAST, at a designated cut-point of 15, was 100 percent, the specificity was 97 percent and the positive predictive value was 50 percent, using the group’s consensus diagnosis as the gold standard. The accuracy indices varied with the case definition used. The sensitivity of the accuracy statistics to case definition and to missing data was explored. The CAST is useful as a screening test for autism spectrum conditions in epidemiological research. There is not currently enough evidence to recommend the use of the CAST as a screening test within a public health screening programme in the general population.
Autism is a severe childhood neuropsychiatric condition with a substantial genetic component. At the cognitive level children with autism are impaired in the development of their folk psychology, seict while they are normal or even superior in the development of their folk physics. We predicted that if their parent shared this cognitive phenotype, then they should be over-represented in engineering as an occupation. This prediction was confirmed. Both fathers and grand-fathers of children with autism were found more than twice as often in the field of engineering, compared with fathers and grandfathers of other children. This link between autism and engineering may throw light not only on autism itself, but ultimately on the genetic basis of two essential human abilities: folk psychology and folk physics.
The Childhood Asperger Syndrome Test (CAST) is a 37-item parental self-completion questionnaire to screen for autism spectrum conditions in research. Good test accuracy was demonstrated in studies with primary school aged children in mainstream schools. The aim of this study was to investigate the test-retest reliability of the CAST. Parents of 1000 children in years 1-6 in five mainstream primary schools in Cambridgeshire received the CAST. A second identical questionnaire was posted to respondents after approximately 2 weeks. Both mailings generated 136 responses. Agreement above and below a screening cut-point of 15 was investigated. The kappa statistic for agreement (< 15 versus > or = 15) was 0.70, and 97 percent (95 percent CI: 93-99 percent) of children did not move across the cut-point of 15. The correlation between the two test scores was 0.83 (Spearman's rho). The CAST has shown good test-retest reliability, and now requires further investigation in a high-scoring sample.
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