DYX1C1 functions in neuronal migration in developing neocortex

Wang, Y.; Paramasivam, M.; Thomas, Ankur; Bai, Jilin; Kaminen‐Ahola, Nina; Kere, Juha; Voskuil, Jan; Rosen, Glenn D.; Galaburda, Albert M.; LoTurco, Joseph J.

doi:10.1016/j.neuroscience.2006.08.022

Cited by 135 publications

(163 citation statements)

References 28 publications

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“…It may be that the associations of DYX1C1 with dyslexia and with short-term memory are mediated by distinct functional effects of mutations in this gene, perhaps by impact on tetratricopeptide repeatdomain mediated neuronal migration. 18 Our significant association for short-term memory closely replicates that reported by Dahdouh et al 28 This group found their result for haplotype rs3743205/rs3743204/rs600753. Of these three SNPS, we measured only marker rs3743204, which, in our sample, was associated with nonword reading, but not with short-term memory (P = 0.82).…”

Section: Discussionsupporting

confidence: 90%

“…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. 30 These data suggest a new candidate for a functional mutation in DYX1C1; given the known role of DYX1C1 in neuronal migration, 17,18 the results bolster the early observation of Galaburda et al 55 that dyslexia may be associated with molecular layer ectopia and microgyria. Marker rs17819126, not typed in previously reported studies and identified here as being associated with reading and spelling, codes for a non-synonymous, exonic protein sequence alteration and warrants the study for its functional role in, especially, neuronal migration.…”

Section: Discussionmentioning

confidence: 52%

“…On the basis of data translocation and association data, 1 and the role of DYX1C1 in neuronal migration, 17,18 we examined the association of SNPs and haplotypes within and near the DYX1C1 gene with well validated and theoretically motivated measures of reading, spelling and shortterm information storage in a large (790 families) sample representative of the general population for reading and spelling ability. Among numerous positive attributes of the study were its size, utilization of normally varying and continuous trait measures assessed over multiple measures, and examination of tagging SNPs for DYX1C1 not previously reported and derived from the HapMap 54 and tested in a population of homogenous and appropriate ethnic origin.…”

Section: Discussionmentioning

confidence: 99%

“…1 Sequence variation analyses suggested that two low-frequency polymorphisms were associated with dyslexia: rs3743205 in the regulatory region of the gene and rs61761345, creating a premature stop codon in the coding region. 1 Molecular-developmental support for DYX1C1 as a gene affecting reading was provided from the finding that, in common with the three other candidate dyslexia genes, DYX1C1 is involved in brain development, in particular in neuronal migration 17,18 and the formation of molecular layer ectopias 19 believed to underlie dyslexia. 20 Despite the translocation and molecular-developmental evidence, and in contrast to KIAA0319 21,22 and DCDC2 23,24 on 6p22, DYX1C1 has not been compellingly shown as affecting variation outside the Finnish families in which it was discovered.…”

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: Discussionmentioning

confidence: 52%

Section: Discussionmentioning

confidence: 99%

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 two strongest SNPs revealed associations with an FDR of 5%, which means that for both SNPs the probability of being a false discovery due to multiple testing is only 5%. Reflecting the candidate approach, all these genes are of high neurobiological relevance: DYX1C1 (dyslexia susceptibility 1 candidate 1) encodes a protein expressed in cortical neurons and white matter glial cells (Taipale et al., 2003) and DYX1C1 contributes to neuronal migration in the developing rodent brain (Wang et al., 2006). ATP2C2 is an ATPase which transports Mg 2+ and Ca 2+ ions into the Golgi lumen for protein modification and is also involved in Ca 2+ signaling (Feng et al., 2010).…”

Section: Discussionmentioning

confidence: 99%

ATP2C2andDYX1C1are putative modulators of dyslexia‐related MMR

et al. 2017

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BackgroundDyslexia is a specific learning disorder affecting reading and spelling abilities. Its prevalence is ~5% in German‐speaking individuals. Although the etiology of dyslexia largely remains to be determined, comprehensive evidence supports deficient phonological processing as a major contributing factor. An important prerequisite for phonological processing is auditory discrimination and, thus, essential for acquiring reading and spelling skills. The event‐related potential Mismatch Response (MMR) is an indicator for auditory discrimination capabilities with dyslexics showing an altered late component of MMR in response to auditory input.MethodsIn this study, we comprehensively analyzed associations of dyslexia‐specific late MMRs with genetic variants previously reported to be associated with dyslexia‐related phenotypes in multiple studies comprising 25 independent single‐nucleotide polymorphisms (SNPs) within 10 genes.ResultsFirst, we demonstrated validity of these SNPs for dyslexia in our sample by showing that additional inclusion of a polygenic risk score improved prediction of impaired writing compared with a model that used MMR alone. Secondly, a multifactorial regression analysis was conducted to uncover the subset of the 25 SNPs that is associated with the dyslexia‐specific late component of MMR. In total, four independent SNPs within DYX1C1 and ATP2C2 were found to be associated with MMR stronger than expected from multiple testing. To explore potential pathomechanisms, we annotated these variants with functional data including tissue‐specific expression analysis and eQTLs.ConclusionOur findings corroborate the late component of MMR as a potential endophenotype for dyslexia and support tripartite relationships between dyslexia‐related SNPs, the late component of MMR and dyslexia.

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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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DYX1C1 functions in neuronal migration in developing neocortex

Cited by 135 publications

References 28 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

ATP2C2andDYX1C1are putative modulators of dyslexia‐related MMR

Molecular Genetics of Dyslexia

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