A family-based association study does not support DYX1C1 on 15q21.3 as a candidate gene in developmental dyslexia

Marino, Cecilia; Giorda, Roberto; Lorusso, Maria Luisa; Vanzin, Laura; Salandi, Nello; Nobile, Maria; Citterio, Andrea; Beri, Silvana; Crespi, Valentina; Battaglia, Marco; Molteni, Massimo

doi:10.1038/sj.ejhg.5201356

Cited by 80 publications

(80 citation statements)

References 34 publications

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“…The two-SNP haplotype (rs61761345 and rs3743205) shown by Taipale et al 1 to influence dyslexia and confirmed by Marino et al 30 for shortmemory measures (but not for dyslexia 37 ) was tested with Mendel. We observed similar haplotype Figure 1 The location of the single-nucleotide polymorphisms (SNPs) tested across the 84-kb region of DYX1C1.…”

Section: Descriptivementioning

confidence: 85%

“…Studies therefore turned to genes in nearby regions, 35 although no candidates have been identified to date, 36 and to the analyses of a small number of additional SNPs in DYX1C1, again without success to date. 37 Thus, although DYX1C1 may be a susceptibility gene for developmental dyslexia, the causal alleles are unknown. Here, we report the first study examining the association of polymorphisms in DYX1C1 with normal variation in reading, examining association at the 2 coding SNPs reported by Taipale et al, 1 and 11 additional tagging SNPs in DYX1C1.…”

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: Descriptivementioning

confidence: 85%

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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“…It is also expressed in human glial and neuronal cells but its function is not known. However, this result is not replicated in a twin cohort and a family-based association study by other investigators (Marino et al 2005;Meng et al 2005a;Bellini et al 2005). To resolve this discrepancy, either more studies are needed or this discrepancy could be due to genetic heterogeneity of dyslexia in different populations.…”

Section: Geneticsmentioning

confidence: 88%

Developmental dyslexia: an update

Shastry

2006

J Hum Genet

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Dyslexia is the most common and carefully studied of the learning disabilities in school-age children. It is characterized by a marked impairment in the development of reading skills, and affects a large number of people (5-10%). Reading difficulties may also arise from poor vision, emotional problems, decreased hearing ability, and behavioral disorders, such as attention-deficit hyperactivity (ADHD). Although many areas of the brain are involved in reading, analysis of postmortem brain specimens by a variety of imaging techniques most consistently suggests that deficiency within a specific component of the language system-the phonologic module-in the temporo-parietal-occipital brain region underlies dyslexia. It is a highly familial and heritable disorder with susceptibility loci on chromosomes 1, 2, 3, 6, 11, 13, 15 and 18. Recently, four candidate genes (KIAA 0319, DYX1C1, DCDC2 and ROBO1) are shown to be associated with dyslexia. Although some of these results are controversial because of the genetic heterogeneity of the disorder, the available evidence suggests that dyslexia could be due to the abnormal migration and maturation of neurons during early development. Interestingly, in spite of genetic heterogeneity, the pathology appears to involve common phonological coding deficits. The condition can be managed by a highly structured educational training exercise.

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“…In this case, the q11 portion of chromosome 15, which had already been identified by linkage analysis and designated DYX1, was translocated onto chromosome 2, and the q21 portion of chromosome 2 was translocated onto chromosome 15 (notated t(2;15)(q11;q21)); analysis of the exact position of the chromosome 15 breakpoint showed that it lay within a previously described gene called EKN1. A small genetic study of families in Finland showed association with EKN1/ DYX1C1 (Taipale et al, 2003), as did a study in Canada (Wigg et al, 2004), but studies in the United States (Meng et al, 2005a) and Italy (Marino et al, 2005) failed to show an association. This implies that the importance of DYX1C1 as a susceptibility gene for RD may be limited to specific populations.…”

Section: Dyx1c1mentioning

confidence: 84%

The human lexinome: Genes of language and reading

Gibson

Gruen

2008

Journal of Communication Disorders

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Within the human genome, genetic mapping studies have identified 10 regions of different chromosomes, known as DYX loci, in genetic linkage with dyslexia, and two, known as SLI loci, in genetic linkage with Specific Language Impairment (SLI). Further genetic studies have identified four dyslexia genes within the DYX loci: DYX1C1 on 15q, KIAA0319 and DCDC2 on 6p22, and ROBO1 on 13q. FOXP2 on 7q has been implicated in the development of Speech-Language Disorder.No genes for Specific Language Impairment have yet been identified within the two SLI loci. Functional studies have shown that all four dyslexia genes play roles in brain development, and ongoing molecular studies are attempting to elucidate how these genes exert their effects at a subcellular level. Taken together, these genes and loci likely represent only a fraction of the human lexinome, a term we introduce here to refer to the collection of all the genetic and protein elements involved in the development of human language, expression, and reading.Learning outcomes: The reader will become familiar with (i) methods for identifying genes for complex diseases, (ii) the application of these methods in the elucidation of genes underlying disorders of language and reading, and (iii) the cellular pathways through which polymorphisms in these genes may contribute to the development of the disorders. #

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A family-based association study does not support DYX1C1 on 15q21.3 as a candidate gene in developmental dyslexia

Cited by 80 publications

References 34 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

Developmental dyslexia: an update

The human lexinome: Genes of language and reading

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