Association of the ROBO1 gene with reading disabilities in a family-based analysis.

Linkage studies have identified a locus on chromosome 3 as reading disabilities (RD) and speech and sound disorder (SSD) susceptibility region, with both RD and SSD sharing similar phonological processing and phonological memory difficulties. One gene in this region, roundabout homolog 1 (ROBO1), has been indicated as a RD candidate and has shown significant association with measures of phonological memory in a population-based sample. In this study, we conducted a family-based association analysis using two independent samples collected in Toronto and Calgary, Canada. Using the two samples, we tested for association between ROBO1 single nucleotide polymorphisms (SNPs) and RD, along with quantitative measures for reading, spelling and phonological memory. One SNP, rs331142, which was selected based on its correlation with ROBO1 expression in brain tissue, was found to be significantly associated with RD in the Toronto sample with over transmission of the minor C allele (P = 0.001), correlated with low expression. This SNP is located ~200 bp from a putative enhancer and results for a marker within the enhancer, rs12495133, showed evidence for association with the same allele in both the Toronto and Calgary samples (P = 0.005 and P = 0.007). These results support previous associations between ROBO1 and RD, as well as correlation with low gene expression, suggesting a possible mechanism of risk conferred by this gene.

A family-based association analysis and meta-analysis of the reading disabilities candidate gene DYX1C1.

Reading disabilities (RD) have a significant genetic basis and have shown linkage to multiple regions including chromosome 15q. Dyslexia susceptibility 1 candidate gene 1 (DYX1C1) on chromosome 15q21 was originally proposed as a candidate gene with two potentially functional polymorphisms at the -3G/A and 1249G/T positions showing association with RD. However, subsequent studies have yielded mixed results. We performed a literature review and meta-analysis of the -3G/A and 1249G/T polymorphisms, including new unpublished data from two family-based samples. Ten markers in DYX1C1 were genotyped in the two independently ascertained samples. Single marker and -3G/A:1249G/T haplotype analyses were performed for RD in both samples, and quantitative trait analyses using standardized reading-related measures was performed in one of the samples. For the meta-analysis, we used a random-effects model to summarize studies that tested for association between -3G/A or 1249G/T and RD. No significant association was found between the DYX1C1 SNPs and RD or any of the reading-related measures tested after correction for the number of tests performed. The previously reported risk haplotype (-3A:1249T) was not biased in transmission. A total of 9 and 10 study samples were included in the meta-analysis of the -3G/A and 1249G/T polymorphisms, respectively. Neither polymorphism reached statistical significance, but the heterogeneity for the 1249G/T polymorphism was high. The results of this study do not provide evidence for association between the putatively functional SNPs -3G/A and 1249G/T and RD.

Association of the dopamine receptor D1 gene, DRD1, with inattention symptoms in families selected for reading problems.

Twin studies have provided evidence for shared genetic influences between attention-deficit/hyperactivity disorder (ADHD) and specific reading disabilities (RD), with this overlap being highest for the inattentive symptom dimension of ADHD. Previously, we found evidence for association of the dopamine receptor D1 gene (DRD1) with ADHD, and with the inattentive symptom dimension in particular. This, combined with evidence for working memory (WM) deficits in individuals with RD or ADHD, and the importance of D1 receptors in attentional processes and WM function, suggests that DRD1 may be a common genetic influence underlying both disorders. Here, in a study of 232 families ascertained through probands with reading problems, we tested for association of the DRD1 gene with RD, as a categorical trait, and with quantitative measures of key reading component skills, WM ability, and inattentive symptoms. Although no associations were found with RD, or with reading component skills or verbal WM, we found evidence for association with inattentive behaviour. Specifically, DRD1 Haplotype 3, the haplotype previously found to be associated with inattentive symptoms in ADHD, is also associated with parent- and teacher-reported symptoms of inattention in this sample selected for reading problems (P=0.023 and 0.004, respectively). Together, the replicated finding of Haplotype 3 association with inattentive symptoms in two independent study samples strongly supports a role for DRD1 in attentional ability. Furthermore, the association of DRD1 with inattention, but not with RD, or the other reading and reading-related phenotypes analysed, suggests that DRD1 contributes uniquely to inattention, without overlap for reading ability.

Support for EKN1 as the susceptibility locus for dyslexia on 15q21.

Dyslexia has been linked to a number of chromosomal regions including 15q. Recently a gene, EKN1, with unknown function in the linked region, was identified via a translocation breakpoint. This gene was further supported as a susceptibility locus by association studies in a Finnish sample. We investigated the possibility of this locus as a susceptibility gene contributing to dyslexia, analyzed as a categorical trait, and analyzed key reading phenotypes as quantitative traits using six polymorphisms including the two previously reported to be associated with dyslexia. In our sample of 148 families identified through a proband with reading difficulties, we found significant evidence for an association to dyslexia analyzed as a categorical trait and found evidence of association to the reading and related processes of phonological awareness, word identification, decoding, rapid automatized naming, language ability, and verbal short-term memory. However, association was observed with different alleles and haplotypes than those reported to be associated in a Finnish sample. These findings provide support for EKN1 as a risk locus for dyslexia and as contributing to reading component processes and reading-related abilities. Based on these findings, further studies of this gene in independent samples are now required to determine the relationship of this gene to dyslexia.

Relation between Kaufman Brief Intelligence Test and WISC-III scores of children with RD.

Concurrent validity of the Kaufman Brief Intelligence Test (K-BIT) with the Wechsler Intelligence Scale for Children-Third Edition (WISC-III) was evaluated, as well as the K-BIT's accuracy as a predictor of WISC-III scores, in a sample of young children with reading disabilities. The two measures were administered to 65 children from Atlanta, Boston, and Toronto who ranged from 6-5 to 7-11 years of age at testing. Correlations between the verbal, nonverbal, and composite scales of the K-BIT and WISC-III were .60, .48, and .63, respectively. Mean K-BIT scores ranged from 1.2 to 5.0 points higher than the corresponding WISC-III scores. Standard errors of estimation ranged from 10.0 to 12.3 points. In individual cases, K-BIT scores can underestimate or overestimate WISC-III scores by as much as 25 points. Results suggest caution against using the K-BIT exclusively for placement and diagnostic purposes with young children with reading disabilities if IQ scores are required.

Remediating the core deficits of developmental reading disability: a double-deficit perspective.

The double-deficit hypothesis (Wolf, 1997; Wolf & Bowers, 1999, this issue) contends that deficits in phonological awareness and deficits in visual naming speed represent two independent causal impediments to reading acquisition for children with developmental reading disabilities (RD). One hundred and sixty-six children with severe RD from 7 to 13 years of age were classified into three deficit subgroups according to a double-deficit framework. A total of 140 children with RD, 84% of the sample, were classified; 54% demonstrated a double deficit (DD), 22% a phonological deficit only (PHON), and 24% a visual-naming speed deficit only (VNS). Diagnostic test profiles highlighted the joint contributions of the two core deficits in depressing written language acquisition. The children in the DD group were more globally impaired than those in the other subgroups, and the VNS group children were the highest achieving and most selectively impaired readers. Following 35 hours of word identification training, sizable gains and significant generalization of training effects were achieved by all subgroups. A metacognitive phonics program resulted in greater generalized effects across the domain of real English words, and a phonological training program produced superior outcomes within the phonological processing domain. The greatest non-word reading gains were achieved by children with only phonological deficits.

Putting struggling readers on the PHAST track: a program to integrate phonological and strategy-based remedial reading instruction and maximize outcomes.

PHAST (for Phonological and Strategy Training) is a research-based remedial reading program that attempts to capitalize upon current research on reading disabilities and their remediation. The focus of the program is on the primary obstacles to word identification learning and independent decoding that most disabled readers face and the steps necessary to help these children achieve independent reading skills. A framework of phonologically based remediation was used as a foundation upon which a set of flexible and effective word identification strategies were scaffolded in an integrated developmental sequence. The program uses a combination of direct instruction and dialogue-based metacognitive training, with the pedagogical emphasis shifting from an initial direct instruction, remedial focus to increasingly metacognitive-strategy-based methods. A continuum of intervention over 70 hours provides both (a) remediation of the basic phonological awareness and letter-sound-learning deficits of disabled readers and (b) specific training of five word identification strategies that offer different approaches to the decoding of unfamiliar words and exposure to different levels of subsyllabic segmentation. Explicit instruction in the application and monitoring of multiple word identification strategies and their application to text-reading activities continues throughout the PHAST Program. PHAST training provides the disabled reader with the opportunity to become a flexible reader who approaches new words in or out of context with multiple strategies and has the ability to evaluate the success of their application. The PHAST Program was developed following the controlled evaluation of its components in laboratory classroom settings and recent positive results from their sequential combination. PHAST represents a new integrated approach to programming in this area using instructional components that have already demonstrated their efficacy with children with severe reading disabilities.

Training and transfer-of-learning effects in disabled and normal readers: evidence of specific deficits.

Two experiments were conducted to assess the specificity of training and transfer deficits in disabled readers, aged 7 to 9 years. Forty-eight children (reading disabled, age-matched normal controls, and reading-level-matched normal controls) participated in both a reading and a nonreading (music) acquisition paradigm. Children received instruction in grapheme-phoneme and symbol-note correspondence patterns, respectively. Posttraining tests (one day and one week) following rule training compared performance on trained exemplar items with performance on untrained transfer items. Results revealed that normal readers were able to transfer their rule knowledge in both the reading and nonreading (music) acquisition paradigms, while disabled readers were proficient only in the music task, and thus demonstrated transfer deficits specific to learning printed language. Transfer was optimally facilitated for all readers when training procedures included not only presentation of exemplars, but also cues for rule derivation and explicit statement of pattern invariances.

Text comprehension training for disabled readers: an evaluation of reciprocal teaching and text analysis training programs.

We are particularly grateful to Dr. Annemarie Sullivan Palincsar for her helpful advice and generosity in sharing materials, procedures, and sample dialogues for use in the version of Reciprocal Teaching used in the present study. This research was supported by an operating grant to the first author from the Ontario Mental Health Foundation. We gratefully acknowledge the contributions of Janet Hinchley and Karen Steinbach in assisting with data collection and Nancy Benson, Carolyn Kroeber, and Karen Steinbach in assisting with data analysis. We thank Sheila Wroblewski and Rosemary Slyne for their contributions in program development and lesson planning. We are grateful to the Principals and staff of Winona and Jesse Ketchem Schools and the Toronto Board of Education for providing satellite locations and support for our programs. The enthusiasm and efforts of the 46 students enrolled in the present programs, and the cooperation and interest of their parents and teachers, are particularly acknowledged.

Computer speech-based training of literacy skills in neurologically impaired children: a controlled evaluation.

Twenty-two reading-disabled children were randomly assigned to one of four training conditions to evaluate the effectiveness of a computer speech-based system for training literacy skills. The sample included 17 children with significant neurological impairment of various etiologies (including spina bifida and hydrocephalus, seizure disorder, brain tumors, cerebral palsy, and head injury) and five developmental dyslexics. The training employed a "talking" computer system that provides synthesized speech feedback during the course of learning. The training conditions included three word recognition and spelling-training programs and a math-training control program. Three different literacy-training procedures were compared, with the size of the trained print-to-sound unit varying as letter-sound (LSD: train-->t/r/ai/n); onset-rhyme (OR: train-->tr/ain) and whole word units (WW: train-->train). All literacy-training groups made significant gains in word recognition and spelling, with the LSD- and OR-trained subjects making the greatest word recognition gains on the words that could be trained with segmented speech feedback (i.e., words with regular spelling-to-sound patterns). All literacy-training groups demonstrated significant transfer on uninstructed rhymes of instructed regular words, with the greatest degree of transfer achieved by the LSD-trained subjects. These findings suggest that the neurologically impaired children were able to profit from instructional procedures that segment the printed word into units corresponding to onsets, rhymes, and phonemes and that this segmentation training may facilitate transfer-of-training for them.

Can dyslexia be treated? Treatment-specific and generalized treatment effects in dyslexic children's response to remediation.

A total of 178 reading disabled children were randomly assigned to one of three treatment conditions providing training in word recognition and decoding skills (DS), oral and written language (OWLS), or classroom survival skills (CSS. an alternative treatment control). Pre- and post-treatment comparisons on an array of standardized and experimental measures indicated that the two experimental treatments (DS, OWLS) resulted in improvement on selected tests significantly greater than that resulting from a third treatment intervention which controlled for treatment time and individual attention (CSS). Effects specific to each experimental treatment were identified, as well as some generalized treatment advantages shared by both experimental groups at post-test. These results indicate that some of the deficits associated with developmental dyslexia are amenable to treatment. Greater generalization of treatment effects was observed following the DS than the OWLS treatment. While DS-instructed children exhibited better word recognition skills, however, their knowledge of grapheme-phoneme correspondence rules was not improved. Several OWLS-specific effects observed on experimental reading and language measures were not replicated on standardized tests which purport to measure the same skills. These results are discussed with respect to (i) possible mechanisms by which disabled readers may acquire word recognition skills, (ii) their failure to acquire and use grapheme-phoneme correspondence rules, and (iii) a possible reduced tendency in the present population to generalize newly acquired specific knowledge to related knowledge domains.

Treatment, subtype, and word type effects in dyslexic children's response to remediation.

Children diagnosed as accuracy-disabled or rate-disabled readers (Lovett, 1984a, 1986, 1987) were randomly assigned to one of three treatment conditions providing training in word recognition and decoding skills (DS), oral and written language (OWLS), or classroom survival skills (an alternative treatment control). The experimental treatment programs exerted a positive treatment effect on the word recognition performances of both groups, but treatment-specific changes in contextual reading and oral language skill were not observed. Pre- and post-treatment comparisons on an experimental word recognition task revealed a post-test advantage for DS-trained children of both subgroups. Accuracy-disabled readers demonstrated treatment-specific gains for both orthographically regular words (e.g., wade) and for exception words (e.g., broad), with their gains greater on exception words. Rate-disabled children demonstrated treatment-specific gains only for exception words, but exhibited these gains following both the DS and the OWLS treatments. Although both experimental treatment programs were associated with a positive outcome for the rate disabled subgroup, DS training was associated with relatively greater treatment gain. These data suggest that the critical variables underlying the effectiveness of the DS treatment include the specific lexical knowledge these disabled readers acquired, their greater reliance on an orthographic pattern procedure in word recognition, and/or the fact that newly acquired items were practiced to a point approximating automatization.

A developmental approach to reading disability: accuracy and speed criteria of normal and deficient reading skill.

The constructs of accuracy and speed were adopted as performance criteria against which to define 2 clinical samples of disabled readers. Accuracy-disabled subjects had failed to achieve reliable age-appropriate word recognition skills. Rate-disabled readers were age-appropriate in word recognition accuracy but deficient in reading speed. These disabled readers were compared to fluent normal children selected to be reading at the same level of accuracy as the rate-disabled subjects but at a significantly faster rate. All aspects of the accuracy-disabled subjects' reading systems proved deficient, and these children were less able to learn new sound-symbol associations in a task simulating initial reading acquisition. The rate-disabled subjects exhibited a basic deficit in word recognition speed, compromised accuracy when reading in context, and compromised spelling when competing visual patterns were available. A multidimensional oral language impairment was found to accompany the accuracy disability, while the rate disability appeared restricted to language in its visible form and the naming of visual representations. A visual naming speed impairment was associated with both profiles of deficient reading skill.

Making reference: the cohesive use of pronouns in the narrative discourse of hemidecorticate adolescents.

The cohesive use of referential language in narrative production reveals communicative goals as well as specific aspects of language use. A formalism for analyzing pronominal cohesion was developed and applied to the narrative discourse of three hemidecorticate adolescents. The results revealed hemisphere-dependent differences in overall narrative skill as well as distinct individual discourse strategies. Neither left hemidecorticate planned narration in extended discourse units: One demonstrated a linear and highly explicit discourse style with redundant over-statement of referent nouns and the other produced narratives cluttered with pronouns of both correct and ambiguous reference, relying on nonpersonal pronouns at considerable cost to narrative specificity. The right hemidecorticate produced narratives that were more economical in form and richer in content: He was the only subject able to maintain simultaneous story lines with multiple pronouns and referential relationships cohesively embedded. All subjects expressed at least some story content, but only the right hemidecorticate narratives conveyed suggestion and implication as well as explicit statement.

Sentential structure and the perceptual spans of two samples of disabled readers.

The constructs of accuracy and speed were adopted as performance criteria against which to define two clinical samples of disabled readers. Accuracy-disabled subjects had failed to achieve reliable age-appropriate word recognition skills. Rate-disabled readers were age-appropriate in word recognition accuracy but deficient on measures of contextual accuracy and reading speed. When their eye-voice spans were measured under different text manipulations, accuracy-disabled and rate-disabled children differed in the magnitude of their perceptual spans during the act of reading. The two samples did not differ in the extent to which they availed themselves of contextual constraints to extend their spans in the reading of connected text. Both samples of disabled readers appeared able to use syntactic information as an independent source of sentential information in reading, even the sample whose reading disability was associated with oral syntax deficits. Comparisons with a previous sample of normal beginning readers suggested both types of disabled readers to be reading with perceptual spans of reduced dimensions.

A developmental perspective on reading dysfunction: accuracy and rate criteria in the subtyping of dyslexic children.

Children referred with specific reading dysfunction were subtyped as accuracy disabled or rate disabled according to criteria developed from an information processing model of reading skill. Multiple measures of oral and written language development were compared for two subtyped samples matched on age, sex, and IQ. The two samples were comparable in reading fluency, reading comprehension, word knowledge, and word retrieval functions. Accuracy disabled readers demonstrated inferior decoding and spelling skills. The accuracy disabled sample proved deficient in their understanding of oral language structure and in their ability to associate unfamiliar pseudowords and novel symbols in a task designed to simulate some of the learning involved in initial reading acquisition. It was suggested that these two samples of disabled readers may be best described with respect to their relative standing along a theoretical continuum of normal reading development.

Sentential structure and the perceptual span in normal reading development.

An eye-voice span paradigm was adopted to determine whether children use different aspects of sentence structure to facilitate decoding early in the course of reading development. Eighty-four Grade 1 and Grade 2 children, representing four levels of early reading competence, and 15 skilled adult subjects read from four textual conditions; materials varied in the extent to which the texts were semantically and/or syntactically constrained. The more precocious the young reader, the longer his reported span. The better readers' and the adults' advantage was greater the more linguistically constrained the reading material. These data support a continuous model of reading development and are compatible with an interactive definition of early reading behavior.

The search for subtypes of specific reading disability: Reflections from a cognitive perspective.

An overview of the literature on developmental dyslexia is offered, moving historically from attempts to identify a single underlying deficit to more recent efforts to define different subtypes of this developmental disorder. Two approaches to the subtyping problem are illustrated and briefly discussed. It is suggested that many of the remaining questions in dyslexia research could be more profitably addressed within the context of a coherent model of reading behaviour. In the latter half of this review, the potential implications of some aspects of the interactive reading theories for the study of reading dysfunction are explored.