A theoretical molecular network for dyslexia: integrating available genetic findings

Poelmans, Geert; Buitelaar, Jan K.; Pauls, David L.; Franke, Barbara

doi:10.1038/mp.2010.105

Cited by 104 publications

(90 citation statements)

References 156 publications

(279 reference statements)

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“…Thus, by including the most significant findings from all disorderspecific GWAS or either linkage studies into their analyses, the work led by Poelmans and colleagues described pathways for neurodevelopmental disorders, including ADHD [110], autism [109] and dyslexia [108]. In these studies, genes related to neurite outgrowth, neural migration and synaptic function were the genetic networks proposed to be predominantly involved in pathophysiology of these disorders.…”

Section: What Do These Findings Tell Us? How Can We Get From Associatmentioning

confidence: 96%

Genetics in child and adolescent psychiatry: methodological advances and conceptual issues

Hohmann

Adamo

Lahey

et al. 2015

Eur Child Adolesc Psychiatry

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Discovering the genetic basis of early-onset psychiatric disorders has been the aim of intensive research during the last decade. We will first selectively summarize results of genetic research in child and adolescent psychiatry by using examples from different disorders and discuss methodological issues, emerging questions and future directions. In the second part of this review, we will focus on how to link genetic causes of disorders with physiological pathways, discuss the impact of genetic findings on diagnostic systems, prevention and therapeutic interventions. Finally we will highlight some ethical aspects connected to genetic research in child and adolescent psychiatry. Advances in molecular genetic methods have led to insights into the genetic architecture of psychiatric disorders, but not yet provided definite pathways to pathophysiology. If replicated, promising findings from genetic studies might in some cases lead to personalized treatments. On the one hand, knowledge of the genetic basis of disorders may influence diagnostic categories. On the other hand, models also suggest studying the genetic architecture of psychiatric disorders across diagnoses and clinical groups.

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Section: What Do These Findings Tell Us? How Can We Get From Associatmentioning

confidence: 96%

Genetics in child and adolescent psychiatry: methodological advances and conceptual issues

Hohmann

Adamo

Lahey

et al. 2015

Eur Child Adolesc Psychiatry

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“…It is a common learning disability affecting about 5%-10% school-aged children in the United States [Shaywitz, 1998]. Although the etiology and pathology of DD remains elusive, there are increasing evidences supporting DD as a genetic disorder [Poelmans et al, 2011]. Initial evidences from linkage studies yielded the identification of nine DD susceptibility loci known as DYX1 to DYX9.…”

Section: Introduction Neuropsychiatric Geneticsmentioning

confidence: 99%

Association study of developmental dyslexia candidate genes DCDC2 and KIAA0319 in Chinese population

Sun

Gao

Zhou

et al. 2014

American J of Med Genetics Pt B

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Developmental dyslexia (DD) is characterized by difficulties in reading and spelling independent of intelligence, educational backgrounds and neurological injuries. Increasing evidences supported DD as a complex genetic disorder and identified four DD candidate genes namely DYX1C1, DCDC2, KIAA0319 and ROBO1. As such, DCDC2 and KIAA0319 are located in DYX2, one of the most studied DD susceptibility loci. However, association of these two genes with DD was inconclusive across different populations. Given the linguistic and genetic differences between Chinese and other populations, it is worthwhile to investigate association of DCDC2 and KIAA0319 with Chinese dyslexic children. Here, we selected 60 tag SNPs covering DCDC2 and KIAA0319 followed by high density genotyping in a large unrelated Chinese cohort with 502 dyslexic cases and 522 healthy controls. Several SNPs (P min ¼ 0.0192) of DCDC2 and KIAA0319 as well as a four-maker haplotype (P adjusted ¼ 0.0289, Odds Ratio (OR) ¼ 1.3400) of KIAA0319 showed nominal association with DD. However, none of these results survived Bonferroni correction for multiple comparisons. Thus, the association of DCDC2 and KIAA0319 with DD in Chinese population should be further validated and their contribution to DD etiology and pathology should be interpreted with caution.

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“…The CGG repeat threshold for specific cognitive disabilities remains to be established and we can hypothesize a link between FMR1, ASFMR1, or genetic factors that modulate FMR1 expression, and dyslexia. Lastly, a recent study proposed a model of biological pathways implicated in dyslexia where nine putative candidate genes, including FMR1 through its interaction with RAC1 protein and FLNA genes, interact in neurons to perform essential functions such as neuritogenesis and neuronal migration (Poelmans et al 2011).…”

Section: Discussionmentioning

confidence: 99%

“…The most relevant genetic model seems to be a complex polygenic model. Nine loci have been linked to dyslexia on chromosomes 15q21 (DYX1), 6p21-p22 (DYX2), 2p15-16 (DYX3), 6q11-q12 (DYX4), 3p11-q13 (DYX5), 18p11 (DYX6), 11p15 (DYX7), 1p34-p36 (DYX8), and Xq26-q27 (DYX9) (for review Scerri and Schulte-Körne 2010;Poelmans et al 2011). The first candidate gene proposed was DYX1C1 (15q21), identified in a kindred with a t(2; 15) (q11; q21) translocation co-segregating with the disorder (Taipale et al 2003).…”

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confidence: 99%

Xq27 FRAXA Locus is a Strong Candidate for Dyslexia: Evidence from a Genome-Wide Scan in French Families

et al. 2013

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Dyslexia is a frequent neurodevelopmental learning disorder. To date, nine susceptibility loci have been identified, one of them being DYX9, located in Xq27. We performed the first French SNP linkage study followed by candidate gene investigation in dyslexia by studying 12 multiplex families (58 subjects) with at least two children affected, according to categorical restrictive criteria for phenotype definition. Significant results emerged on Xq27.3 within DYX9. The maximum multipoint LOD score reached 3,884 between rs12558359 and rs454992. Within this region, seven candidate genes were investigated for mutations in exonic sequences (CXORF1, CXORF51, SLITRK2, FMR1, FMR2, ASFMR1, FMR1NB), all having a role during brain development. We further looked for 5 0 UTR trinucleotide repeats in FMR1 and FMR2 genes. No mutation or polymorphism co-segregating with dyslexia was found. This finding in French families with Dyslexia showed significant linkage on Xq27.3 enclosing FRAXA, and consequently confirmed the DYX9 region as a robust susceptibility locus. We reduced the previously described interval from 6.8 (DXS1227-DXS8091) to 4 Mb also disclosing a higher LOD score.

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A theoretical molecular network for dyslexia: integrating available genetic findings

Cited by 104 publications

References 156 publications

Genetics in child and adolescent psychiatry: methodological advances and conceptual issues

Genetics in child and adolescent psychiatry: methodological advances and conceptual issues

Association study of developmental dyslexia candidate genes DCDC2 and KIAA0319 in Chinese population

Xq27 FRAXA Locus is a Strong Candidate for Dyslexia: Evidence from a Genome-Wide Scan in French Families

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