Evaluation of candidate genes for <i>DYX1</i> and <i>DYX2</i> in families with dyslexia

Brkanac, Zoran; Chapman, Nicola H.; Matsushita, Mark; Chun, Lani S.; Nielsen, Kathleen; Cochrane, Elizabeth; Berninger, Virginia W.; Wijsman, Ellen M.; Raskind, Wendy H.

doi:10.1002/ajmg.b.30471

Cited by 80 publications

(104 citation statements)

References 31 publications

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“…The results did not support association for the two SNPs reported as associated with dyslexia in Finnish readers. 1 These findings are consistent both with other data, suggesting that the association of markers rs3743205 and rs61761345 identified by Taipale et al may be specific to the Finnish genetic background 4 and with other data suggesting that DYX1C1 is nevertheless associated with reading disability in non-Finnish populations, 28,31 as well as with short-term memory. 28,30 Overall, these data significantly increase support for a role of DYX1C1 in dyslexia and, perhaps separately, in short-term storage of verbal information.…”

Section: Discussionsupporting

confidence: 90%

“…29 The effect was mostly accounted for by an association with short-term memory, supporting the finding of Marino et al 30 that the SNPs reported by Taipale may be related more to short-term memory than to dyslexia. Brkanac et al 31 recently reported a nominally significant association of rs61761345 in a sample of 191 dyslexic probands, together with their parental and matched unrelated controls.…”

Section: Introductionmentioning

confidence: 99%

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Dyslexia and DYX1C1: deficits in reading and spelling associated with a missense mutation

Bates

Lind²,

Luciano

et al. 2009

Mol Psychiatry

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The status of DYX1C1 (C15q21.3) as a susceptibility gene for dyslexia is unclear. We report the association of this gene with reading and spelling ability in a sample of adolescent twins and their siblings. Family-based association analyses were carried out on 13 single-nucleotide polymorphisms (SNPs) in DYX1C1, typed in 790 families with up to 5 offspring and tested on 6 validated measures of lexical processing (irregular word) and grapheme-phoneme decoding (pseudo-word) reading-and spelling-based measures of dyslexia, as well as a short-term memory measure. Significant association was observed at the misssense mutation rs17819126 for all reading measures and for spelling of lexical processing words, and at rs3743204 for both irregular and nonword reading. Verbal short-term memory was associated with rs685935. Support for association was not found at rs3743205 and rs61761345 as previously reported by Taipale et al., but these SNPs had very low (0.002 for rs3743205) minor allele frequencies in this sample. These results suggest that DYX1C1 influences reading and spelling ability with additional effects on short-term information storage or rehearsal. Missense mutation rs17819126 is a potential functional basis for the association of DYX1C1 with dyslexia.

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Section: Discussionsupporting

confidence: 90%

Section: Introductionmentioning

confidence: 99%

Dyslexia and DYX1C1: deficits in reading and spelling associated with a missense mutation

Bates

Lind²,

Luciano

et al. 2009

Mol Psychiatry

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Section: Tran Et Al 151mentioning

confidence: 99%

“…In a family-based association study by Wigg et al [2004], a different marker rs11629841 was found to be significantly associated with RD which was in high LD with both À3G/A and 1249G/T. Brkanac et al [2007] found association with the 1249G/T polymorphism, but it was the major G allele that was overtransmitted, rather than the T allele which showed association in the study by Taipale et al [2003]. A number of other studies did not find association between DYX1C1 SNPs and RD [Bellini et al, 2005;Cope et al, 2005;Marino et al, 2005;Saviour et al, 2008;Newbury et al, 2011;Venkatesh et al, 2011].…”

Section: Introductionmentioning

confidence: 99%

“…The most common test that was used to assess intelligence was the Wechsler Intelligence Scale for Children. Five of the samples also reported the use of neurological, medical or sensorial disorders as exclusionary criteria, although the specific disorders that were screened varied across the samples [Bellini et al, 2005;Brkanac et al, 2007;Marino et al, 2007;Newbury et al, 2011] (Toronto sample, this study).Within the pooled case-control studies, a total of 786 cases and 756 controls were included. For one study, the allele frequencies in two independent samples were compared to the same group of controls but for the meta-analysis, the controls were only counted once [Newbury et al, 2011].…”

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confidence: 99%

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

Tran

Gagnon

Wigg

et al. 2013

American J of Med Genetics Pt B

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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 À3G/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 À3G/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 À3G/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 À3G/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 (À3A:1249T) was not biased in transmission. A total of 9 and 10 study samples were included in the meta-analysis of the À3G/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 À3G/A and 1249G/T and RD. Ó 2013 Wiley Periodicals, Inc.Key words: dyslexia; chromosome 15q; EKN1; genetics INTRODUCTIONSpecific reading disabilities (RD), or developmental dyslexia, refer to an unexpected and specific difficulty in learning to read despite normal or above average intelligence, education, and socioeconomic opportunity. RD is likely caused by a dysfunction of neural systems involved in cognitive skills required for reading [Habib, 2000]. A core deficit observed in dyslexics involves the processing of phonemes, the most basic unit of speech sounds, which persist into adulthood [Bruck, 1992;Shaywitz et al., 1999;Ramus et al., 2003]. Individuals with RD have difficulty segmenting words into their phonological elements, impairing their ability in learning to read. Several other reading components have been shown to be impaired in individuals with RD including orthographic coding, single-word reading, rapid automatic naming, and spelling [Denckla and Rudel, 1976;Paulesu et al., 2001;Francks et al., 2002]. With an estimated Additional supporting information may be found in the online version of this article. 146Neuropsychiatric Genetics prevalence ranging from 5% to 17.5% in school-aged children, RD is the most common learning disability and affects four out of five individuals with learning disabilities [Shaywitz et al., 1990;Shaywitz, 1998;Katusic et al., 2001]. There is substantial evidence to suggest that RD is both familial and heritable. RD has bee...

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Molecular Genetics of Dyslexia

Paracchini

2009

Encyclopedia of Life Sciences

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Dyslexia is a specific impairment in learning to read which affects 5–10% of school‐age children. Family and twin studies have shown that dyslexia is caused in large part by genetic factors. Dyslexia is most likely the result of the interplay of multiple genetic and environmental factors. Recently, several genes have been proposed as candidates for dyslexia susceptibility, including DYX1C1 on chromosome 15, KIAA0319 and DCDC2 on chromosome 6, ROBO1 on chromosome 3 and MRPL19 and C2ORF3 on chromosome 2. Interestingly, these genes share a putative role in brain development. No functional genetic variant has been identified for any of the genes but the study of their function offers for the first time new insights in the understanding of the biology of dyslexia and the mechanisms underlying cognition and brain function. Key concepts Several genes have recently been proposed as candidates for dyslexia susceptibility. Most of these genes have shown association in independent samples of individuals with dyslexia. A specific risk haplotype has been identified for the KIAA0319 gene. Most of the candidates have been implicated in brain development. No functional mutations have been identified for any of the genes. Gene expression has been proposed as the main mechanism linking genetic susceptibility to the development of dyslexia

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Evaluation of candidate genes for DYX1 and DYX2 in families with dyslexia

Cited by 80 publications

References 31 publications

Dyslexia and DYX1C1: deficits in reading and spelling associated with a missense mutation

Dyslexia and DYX1C1: deficits in reading and spelling associated with a missense mutation

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

Molecular Genetics of Dyslexia

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