Multipoint genome-wide linkage scan for nonword repetition in a multigenerational family further supports chromosome 13q as a locus for verbal trait disorders

Abstract

Verbal trait disorders encompass a wide range of conditions and are marked by deficits in five domains that impair a person’s ability to communicate: speech, language, reading, spelling, and writing. Nonword repetition is a robust endophenotype for verbal trait disorders that is sensitive to cognitive processes critical to verbal development, including auditory processing, phonological working memory, and motor planning and programming. In the present study, we present a six-generation extended pedigree with a history of verbal trait disorders. Using genome-wide multipoint variance component linkage analysis of nonword repetition, we identified a region spanning chromosome 13q14–q21 with LOD = 4.45 between 52 and 55 cM, spanning approximately 5.5 Mb on chromosome 13. This region overlaps with SLI3, a locus implicated in reading disability in families with a history of specific language impairment. Our study of a large multigenerational family with verbal trait disorders further implicates the SLI3 region in verbal trait disorders. Future studies will further refine the specific causal genetic factors in this locus on chromosome 13q that contribute to language traits.Electronic supplementary materialThe online version of this article (doi:10.1007/s00439-016-1717-z) contains supplementary material, which is available to authorized users.

A frequent acoustic sign of speech motor delay (SMD)

“…In the present study, the high percentage of children with SMD with increased durations of vowels that are not difficult to articulate could reflect transcoding (planning/programming) deficits associated with stress that are similar to the transcoding deficits proposed in CAS (Shriberg et al, 2017b). The likelihood of identifying causal genes and copy number variants for SMD that confer risk for pleiotropic effects within and among speech, language, and motor domains is consistent with contemporary trends in genomic research in verbal trait disorders (e.g., Lewis, Iyengar, & Stein, 2018;Miscimarra et al, 2007;Peter, Matsushita, & Raskind, 2012;Smith, Pennington, Boada, & Shriberg, 2005;Stein et al, 2006Stein et al, , 2004Truong et al, 2016).…”

Estimates of the prevalence of motor speech disorders in children with idiopathic speech delay

“…As described in reviews of the many explanatory accounts of what are now termed S peech Sound Disorders (i.e., excluding dysfluency) and the treatment approaches consistent with these accounts, the dominant theoretical frameworks are variants of a neurocognitive perspective that developmental delays in encoding and retrieving linguistic representations are the core deficits underlying speech sound deletions and substitutions (c.f., Baker, Williams, McLeod, & McCauley, 2018; Bernthal, Bankson, & Flipsen, 2017; Bowen, 2015; McLeod & Baker, 2017; Rvachew & Brosseau-Lapré, 2018). Substantial genetic and behavioural support for this perspective has been provided by findings indicating that idiopathic speech sound disorders are associated with disabilities in four other heritable verbal traits: language, reading, writing, and spelling (e.g., Lewis et al, 2011; Truong et al, 2016). As discussed presently, the classification system in this paper uses the term Speech Delay (SD) for one of two classes of speech sound disorders of known or unknown (idiopathic) origin defined by the presence of age-inappropriate speech sound deletions and/or substitutions.…”

“…Some new terms and minor changes in Figure 1 replace terms in prior versions of the SDCS. As indicated by the solid border, the etiological subtype termed Speech Delay-Genetic has been widely supported in genetic studies of idiopathic speech-language and other verbal trait disorders (e.g., Deriziotis & Fisher, 2017; Eising et al, 2018; Guerra & Cacabelos, 2018; Truong et al, 2016). In comparison, two proposed etiological subtypes of SD – SD associated with early recurrent otitis media with effusion (SD-OME) and SD associated with developmental psychosocial involvement – have dashed border lines indicating that they currently are considered risk factors for SD.…”

Estimates of the prevalence of speech and motor speech disorders in adolescents with Down syndrome

“…The Method section and a Supplement for this research series [Supplementary Data] provide detailed information on methods and measures in the finalized version of a classification system termed the Speech Disorders Classification System (SDCS) developed for research in childhood speech sound disorders (Shriberg, Kwiatkowski, & Mabie, 2019). The SDCS, which provides the research framework for the present study, has been used to classify participants’ motor speech status in a number of studies of the genomic and behavioural substrates of persons with speech sound disorders (e.g., Baylis & Shriberg, 2018; Eising et al, 2018; Laffin et al, 2012; Raca et al, 2013; Redle et al, 2015; Rice et al, 2012; Shriberg, Jakielski, & El-Shanti, 2008; Shriberg, Paul, Black, & van Santen, 2011; Shriberg, Potter, & Strand, 2011; Truong et al, 2016; Worthey et al, 2013).…”