Association of short‐term memory with a variant within DYX1C1 in developmental dyslexia

Abstract

A substantial genetic contribution in the etiology of developmental dyslexia (DD) has been well documented with independent groups reporting a susceptibility locus on chromosome 15q. After the identification of the DYX1C1 gene as a potential candidate for DD, several independent association studies reported controversial results. We performed a family-based association study to determine whether the DYX1C1 single nucleotide polymorphisms (SNPs) that have been associated with DD before, that is SNPs '23GA' and '1249GT', influence a broader phenotypic definition of DD. A significant linkage disequilibrium was observed with 'Single Letter Backward Span' (SLBS) in both single-marker and haplotype analyses. These results provide further support to the association between DD and DYX1C1 and it suggests that the linkage disequilibrium with DYX1C1 is more saliently explained in Italian dyslexics by short-term memory, as measured by 'SLBS', than by the categorical diagnosis of DD or other related phenotypes.

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

“…Our finding suggests that this gene is not sex-limited, but may be more readily detected in younger females compared with young males because of the higher heritability of dyslexia in younger females. 29 The effect was mostly accounted for by 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.…”

“…This may reflect a sex-limited gene effect, or the higher heritability of dyslexia in females. 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.…”

“…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. 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.…”

“…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.…”

“…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.…”