Evidence for a susceptibility locus on chromosome 6q influencing phonological coding dyslexia

Am J Med Genet. 2001 Aug 8;105(6):507-17. doi: 10.1002/ajmg.1475.


A linkage study of 96 dyslexia families containing at least two affected siblings (totaling 877 individuals) has found evidence for a dyslexia susceptibility gene on chromosome 6q11.2-q12 (assigned the name DYX4). Using a qualitative phonological coding dyslexia (PCD) phenotype (affected, unaffected, or uncertain diagnoses), two-point parametric analyses found highly suggestive evidence for linkage between PCD and markers D6S254, D6S965, D6S280, and D6S251 (LOD(max) scores = 2.4 to 2.8) across an 11 cM region. Multipoint parametric analysis supported linkage of PCD to this region (peak HLOD = 1.6), as did multipoint nonparametric linkage analysis (P = 0.012). Quantitative trait linkage analyses of four reading measures (phonological awareness, phonological coding, spelling, and rapid automatized naming speed) also provided evidence for a dyslexia susceptibility locus on chromosome 6q. Using a variance-component approach, analysis of phonological coding and spelling measures resulted in peak LOD scores at D6S965 of 2.1 and 3.3, respectively, under 2 degrees of freedom. Furthermore, multipoint nonparametric quantitative trait sibpair analyses suggested linkage between the 6q region and phonological awareness, phonological coding, and spelling (P = 0.018, 0.017, 0.0005, respectively, for unweighted sibpairs < 18 years of age). Although conventional significance thresholds were not reached in the linkage analyses, the chromosome 6q11.2-q12 region clearly warrants investigation in other dyslexia family samples to attempt replication and confirmation of a dyslexia susceptibility gene in this region.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Child
  • Chromosomes, Human, Pair 6 / genetics*
  • Dyslexia / genetics*
  • Family Health
  • Female
  • Genetic Linkage
  • Genetic Predisposition to Disease / genetics*
  • Haplotypes
  • Humans
  • Linkage Disequilibrium
  • Lod Score
  • Male
  • Microsatellite Repeats
  • Nuclear Family
  • Phenotype