Developmental dyslexia is a neurofunctional disorder characterised by an unexpected diYculty in learning to read and write despite adequate intelligence, motivation, and education. Previous studies have suggested mostly quantitative susceptibility loci for dyslexia on chromosomes 1, 2, 6, and 15, but no genes have been identified yet. We studied a large pedigree, ascertained from 140 families considered, segregating pronounced dyslexia in an autosomal dominant fashion. AVected status and the subtype of dyslexia were determined by neuropsychological tests. A genome scan with 320 markers showed a novel dominant locus linked to dyslexia in the pericentromeric region of chromosome 3 with a multipoint lod score of 3.84. Nineteen out of 21 aVected pedigree members shared this region identical by descent (corrected p<0.001). Previously implicated genomic regions showed no evidence for linkage. Sequencing of two positional candidate genes, 5HT1F and DRD3, did not support their role in dyslexia. The new locus on chromosome 3 is associated with deficits in all three essential components involved in the reading process, namely phonological awareness, rapid naming, and verbal short term memory. (J Med Genet 2001;38:658-664)

Developmental dyslexia is a distinct learning disability with unexpected difficulty in learning to read despite adequate intelligence, education, and environment, and normal senses. The genetic aetiology of dyslexia is heterogeneous and loci on chromosomes 2, 3, 6, 15, and 18 have been repeatedly linked to it. We have conducted a genome scan with 376 markers in 11 families with 38 dyslexic subjects ascertained in Finland. Linkage of dyslexia to the vicinity of DYX3 on 2p was confirmed with a nonparametric linkage (NPL) score of 2.55 and a lod score of 3.01 for a dominant model, and a novel locus on 7q32 close to the SPCH1 locus was suggested with an NPL score of 2.77. The SPCH1 locus has previously been linked with a severe speech and language disorder and autism, and a mutation in exon 14 of the FOXP2 gene on 7q32 has been identified in one large pedigree. Because the language disorder associated with the SPCH1 locus has some overlap with the language deficits observed in dyslexia, we sequenced the coding region of FOXP2 as a candidate gene for our observed linkage in six dyslexic subjects. No mutations were identified. We conclude that DYX3 appears to be important for dyslexia susceptibility in many Finnish families, and a suggested linkage of dyslexia to chromosome 7q32 will need verification in other data sets. D evelopmental dyslexia is a distinct learning disability with unexpected difficulty in learning to read despite adequate intelligence, education, environment, and normal senses. The impairment in dyslexia appears to be in phonological processing, which interferes with the function of the linguistic system at the higher level, such as semantics.1 Functional brain imaging studies have shown that dyslectic subjects have a common neuroanatomical basis.2 Dyslexia is relatively common affecting 5-10% of the population depending on the definition.3 Previous twin and family studies have established a large genetic component in the aetiology of dyslexia. 4 Although at least two loci have shown clearly dominant transmission (DYX3 and DYX5), the mode of inheritance seems to be non-Mendelian for other loci. Therefore, the aetiology of dyslexia is likely to be heterogeneous 5 and at least five loci have consistently been linked to dyslexia: DYX1 on 15q21, DYX2 on 6p21.3, DYX3 on 2p16-p15, DYX5 on 3p12-q13, and DYX6 on 18p11.2 (http//www.ncbi.nlm.nih.gov/omim).The first gene associated with speech and language development, FOXP2 (forkhead box P2) on 7q31, was identified through a large pedigree, the KE family, with half of the family members affected by a severe speech and language disorder (SPCH1). 6 They have mainly problems in articulation, expressive speech, and grammar, but also impairment in phonological processing is detected.7 8 All affected subjects have a G to A nucleotide transition in exon 14 of FOXP2. In addition, an unrelated subject with a similar phenotype has a de novo balanced reciprocal translocation t(5;7)(q22;q31.2) mapping specifically to an intron between exons 3b and 4 of FOXP2. 9The FOXP2 ...

Developmental dyslexia is characterised by diYculties in learning to read. As reading is a complex cognitive process, multiple genes are expected to contribute to the pathogenesis of dyslexia. The genetics of dyslexia has been a target of molecular studies during recent years, but so far no genes have been identified. However, a locus for dyslexia on chromosome 15q21 (DYX1) has been established in previous linkage studies. We have identified two families with balanced translocations involving the 15q21-q22 region. In one family, the translocation segregates with specific dyslexia in three family members. In the other family, the translocation is associated with dyslexia in one family member. We have performed fluorescence in situ hybridisation (FISH) studies to refine the position of the putative dyslexia locus further. Our results indicate that both translocation breakpoints on 15q map within an interval of approximately 6-8 Mb between markers D15S143 and D15S1029, further supporting the presence of a locus for specific dyslexia on 15q21. (J Med Genet 2000;37:771-775) Keywords: dyslexia; reading disability; chromosome 15; translocation Specific reading disability or developmental dyslexia is an unexpected diYculty in learning to read despite adequate intelligence, education, and normal senses. It is regarded as a language based disorder that usually reflects insuYcient phonological processing abilities. 1The prevalence of dyslexia ranges from 3 to 15% of the population and about 4% are seriously aVected. 2Developmental dyslexia is a heterogeneous clinical condition. The risk for reading impairment is greater in relatives of dyslexia probands than in the general population.3 4 The phenotype of dyslexia is variable and diVerent subtypes can be distinguished. Reading is a complex cognitive process and consequently multiple genes of relatively small eVects are expected to contribute to its variability. 5Previous linkage studies have implicated four diVerent chromosomal areas harbouring dyslexia loci/genes. The pericentromeric region of chromosome 15 was the first locus suggested to be linked to dyslexia.6 These results were later questioned and linkage to chromosome 1p34-p36 was suggested. The authors suggested that their positive linkage result to 15q21 (two point lod score 1.26 at =0 with marker D15S143, maximum multipoint lod score 2.19 at marker D15S143) verified this region as an established locus for dyslexia (DYX1).11 In an extended Norwegian pedigree, a fourth locus for dyslexia was recently identified on chromosome 2p15-p16. 12 We describe here one family in which a translocation t(2;15)(q11;q21) cosegregates with reading problems in four translocation carriers. In another family, a translocation t(2;15)(p13;q22) associates with dyslexia in one family member but not in three other translocation carriers. Even though both translocation breakpoints were originally assigned to diVerent chromosomal bands but close to the DYX1 locus on chromosome 15, we performed a FISH analysis to refine the chromos...

There are two main methodologies for constructing the knowledge base of a natural language analyser: the linguistic and the data-driven. Recent state-of-the-art part-of-speech taggers are based on the data-driven approach. Because of the known feasibility of the linguistic rule-based approach at related levels of description, the success of the data-driven approach in part-of-speech analysis may appear surprising. In this paper 1 , a case is made for the syntactic nature of part-of-speech tagging. A new tagger of English that uses only linguistic distributional rules is outlined and empirically evaluated. Tested against a benchmark corpus of 38,000 words of previously unseen text, this syntax-based system reaches an accuracy of above 99%. Compared to the 95-97% accuracy of its best competitors, this result suggests the feasibility of the linguistic approach also in part-of-speech analysis.

This is the first nationwide register-based study to examine the relationship between prenatal maternal smoking and Tourette syndrome. A total of 767 children diagnosed with Tourette syndrome were identified from the Finnish Hospital Discharge Register. Each case was matched to four controls. Information on maternal smoking during pregnancy was obtained from the Finnish Medical Birth Register. Conditional logistic regression models were used for statistical analyses. Prenatal maternal smoking was associated with Tourette syndrome when comorbid with ADHD (OR 4.0, 95 % CI 1.2-13.5, p = 0.027 for exposure during first trimester, OR 1.7, 95 % CI, 1.05-2.7, p = 0.031 for exposure for the whole pregnancy). There was no association between maternal smoking during pregnancy and Tourette syndrome without comorbid ADHD (OR 0.5, 95 % CI 0.2-1.3, p = 0.166, OR 0.9, 95 % CI 0.7-1.3, p = 0.567). Further research is needed to elucidate the mechanisms behind the association between prenatal maternal smoking and Tourette syndrome with comorbid ADHD.