ABSTRACT
Specific reading disabilities (RD), also known as developmental dyslexia, is a major educational, social and mental health issue. RD is a specific learning disability, characterized by difficulties with fluent word recognition, and by poor spelling and decoding abilities (Lyon 2003). Three to 6% of otherwise normally developing children demonstrate this developmental neurocognitive disorder, and deficits often persist into adulthood. For many years RD has been known to be familial and evidence from twin studies indicates that RD has a substantial genetic component. Genetic studies have found evidence for linkage, or association, to chromosomes 1p34-p36 (Rabin et al. 1993; Grigorenko et al. 2001; Tzenova et al. 2004), 2p11 (Kaminen et al. 2003), 2p15-16 (Fagerheim et al. 1999; Fisher et al. 2002; Petryshen et al. 2002; Francks et al. 2004), 3p12-q13 (Nopola-Hemmi et al. 2001; Stein et al. 2004), 6p21.3-22 (Smith and Kimberling 1991; Cardon et al. 1994; Grigorenko et al. 1997; Gayan et al. 1999; Kaplan et al. 2002; Grigorenko et al. 2003; Turic et al. 2003; Deffenbacher et al. 2004; Francks et al. 2004; Cope et al. 2005a), 6q11.2-q12 (Petryshen et al. 2001), 7q32 (Kaminen et al. 2003), 11p15.5 (Fisher et al. 2002; Hsiung et al. 2004), 15q (Smith et al. 1983; Smith et al. 1991; Grigorenko et al. 1997; Morris et al. 2000), and 18p11.2 (Fisher et al. 2002; Marlow et al. 2003). There has been unprecedented replication of linkage findings for this complex trait, for the loci on chromosomes 2, 6, and 15, however these have not replicated in all studies. At this point it is not clear if the failure to replicate is due to power, phenotypic (large families, age of the subjects, ascertainment strategy, ethnic composition) or
locus heterogeneity. Furthermore, the possibility of false positive results for some of the linkage reports cannot be ruled out, until further confirmatory replication studies. Fine mapping studies have begun and some of these chromosomal regions have been sufficiently narrowed to allow for gene identification. On chromosome 15q21, a chromosomal translocation breakpoint has identified a gene, EKN1 (DYX1C1), which may be the first gene identified contributing to RD (Taipale et al. 2003). At the current time, the evidence for this gene as contributing to RD has not been supported in all samples, and it remains unclear if this is the susceptibility gene on 15q. In the other linked chromosomal regions, fine-mapping studies will undoubtedly lead to gene identification in the next few years. These gene findings will be the first step in understanding the neurobiology underlying this uniquely human, cognitive process.
