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

A linkage study of 96 dyslexia families containing at least two affected si blings (totaling 877 individuals) has found evidence for a dyslexia suscept ibility gene on chromosome 6q11.2-q12 (assigned the name DYX4). Using a qua litative phonological coding dyslexia (PCD) phenotype (affected, unaffected , or uncertain diagnoses), two-point parametric analyses found highly sugge stive evidence for linkage between PCD and markers D6S254, D6S965, D6S280, and D6S251 (LODmax scores=2.4 to 2.8) across an 11 cM region. Multipoint pa rametric analysis supported linkage of PCD to this region (peak HLOD = 1.6) , as did multipoint nonparametric linkage analysis (P = 0.012). Quantitativ e trait linkage analyses of four reading measures (phonological awareness, phonological coding, spelling, and rapid automatized naming speed) also pro vided 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, respectivel y, under 2 degrees of freedom. Furthermore, multipoint nonparametric quanti tative trait siblingpair analyses suggested linkage between the 6q region a nd phonological awareness, phonological coding, and spelling (P = 0.018, 0. 017, 0.0005, respectively, for unweighted sibpairs <18 years of age). Altho ugh conventional significance thresholds were not reached in the linkage an alyses, 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. (C) 2001 Wiley-Liss, Inc.