Speech Sound Disorder Influenced by a Locus in 15q14 Region

Abstract

Despite a growing body of evidence indicating that speech sound disorder (SSD) has an underlying genetic etiology, researchers have not yet identified specific genes predisposing to this condition. The speech and language deficits associated with SSD are shared with several other disorders, including dyslexia, autism, Prader-Willi Syndrome (PWS), and Angelman's Syndrome (AS), raising the possibility of gene sharing. Furthermore, we previously demonstrated that dyslexia and SSD share genetic susceptibility loci. The present study assesses the hypothesis that SSD also shares susceptibility loci with autism and PWS. To test this hypothesis, we examined linkage between SSD phenotypes and microsatellite markers on the chromosome 15q14-21 region, which has been associated with autism, PWS/AS, and dyslexia. Using SSD as the phenotype, we replicated linkage to the 15q14 region (P=0.004). Further modeling revealed that this locus influenced oral-motor function, articulation and phonological memory, and that linkage at D15S118 was potentially influenced by a parent-of-origin effect (LOD score increase from 0.97 to 2.17, P=0.0633). These results suggest shared genetic determinants in this chromosomal region for SSD, autism, and PWS/AS.

Genes, language development, and language disorders

“…SSD phenotypes have shown linkage to three dyslexia candidate regions, DYX5 (chromosome 3p12) [Stein et al, 2004], DYX2 (6p22) and two regions on chromosome 15 that have been associated with dyslexia: 15q21 and 15q14 [Stein et al, 2006]. As with ADHD, confirmation that the two disorders may be caused by the same genes depends on finding the actual genes involved.…”

Children with Comorbid Speech Sound Disorder and Specific Language Impairment are at Increased Risk for Attention-Deficit/Hyperactivity Disorder

“…Recent molecular genetics analyses have heightened interest in the comorbidity of RD, ADHD, and SSD because all three disorders have shown linkage to the same genetic locus at 6p22 (Fisher and DeFries 2002;Smith et al 2005;Willcutt et al 2002). Additionally, several studies have identified loci that are pleiotropic for RD and ADHD (Bakker et al 2003;Gayan et al 2005;Loo et al 2004) and RD and SSD (Miscimarra et al 2007;Smith et al 2005;Stein et al 2004Stein et al , 2006. This preliminary evidence for shared genetic risk factors suggests that all three disorders may overlap phenotypically, to some extent.…”

Multivariate Linkage Analysis of Specific Language Impairment (SLI)

“…These studies have all been performed using families affected by speech-sound disorder (SSD), characterised by developmentally inappropriate errors in speech production and considered to be a phonological subtype of SLI (Stein et al 2004(Stein et al , 2006Smith et al 2005). The first study of SSD (Stein et al 2004) focussed upon a region of chromosome 3 previously implicated in dyslexia (DYX5 [MIM606896]).…”

“…Evidence for linkage was also found using the reading scores (P < 0.006). The same set of families were also used in an investigation of a region of chromosome 15q which is deleted in Prader-Willi and Angelman Syndromes and has been linked to both autism (AUTS4 [MIM209850]) and dyslexia (DYX1 [MIM127700]) (Stein et al 2006). The factor scores were not employed in this study, but instead an affected sib-pair analysis was performed using a binary affection status.…”