Robust Candidates for Language Development and Evolution Are Significantly Dysregulated in the Blood of People With Williams Syndrome.

Antonio Benítez-Burraco,Ryo Kimura

doi:10.3389/fnins.2019.00258

Antonio Benítez-Burraco, Ryo Kimura

Open Access

https://doi.org/10.3389/fnins.2019.00258

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Abstract

Williams syndrome (WS) is a clinical condition, involving cognitive deficits and an uneven language profile, which has been the object of intense inquiry over the last decades. Although WS results from the hemideletion of around two dozen genes in chromosome 7, no gene has yet been probed to account for, or contribute significantly to, the language problems exhibited by the affected people. In this paper we have relied on gene expression profiles in the peripheral blood of WS patients obtained by microarray analysis and show that several robust candidates for language disorders and/or for language evolution in the species, all of them located outside the hemideleted region, are up- or downregulated in the blood of subjects with WS. Most of these genes play a role in the development and function of brain areas involved in language processing, which exhibit structural and functional anomalies in people with this condition. Overall, these genes emerge as robust candidates for language dysfunction in WS.

Highlights

Williams syndrome (WS) is a clinical condition resulting from a hemizygous deletion of 1.5 to 1.8 Mb on 7q11.23, which encompasses nearly 30 genes (Korenberg et al, 2000; Pober et al, 2010)
We found that candidates for language development and language evolution are significantly dysregulated in the blood of subjects with WS (p = 1.1e-7 by Fisher’s exact test)
The gene has been related to neuronal migration and neurite outgrowth anomalies linked to developmental dyslexia (DD) (Shao et al, 2016), it is associated with autism spectrum disorder (ASD) (Pagnamenta et al, 2010) and SZ (Alkelai et al, 2012)

Summary

Introduction

Williams syndrome (WS) is a clinical condition resulting from a hemizygous deletion of 1.5 to 1.8 Mb on 7q11.23, which encompasses nearly 30 genes (Korenberg et al, 2000; Pober et al, 2010). Regarding LIMK1, it regulates synaptic plasticity and long-term memory (Todorovski et al, 2015), and its hemideletion has been hypothesized to account for the observed deficits in spatial cognition in combination with other genes (Gray et al, 2006; Smith et al, 2009) Still, these potential links with aspects of language (dys)function seem quite vague, if one considers our remarkable understanding of the genetic underpinnings of human language, language disorders, and language evolution (see Scharff and White, 2004; Li and Bartlett, 2012; Benítez-Burraco, 2013; Graham et al, 2015; Fisher, 2017; Murphy and BenítezBurraco, 2017, 2018 for reviews). They found BCL11A, a gene associated with speech disorders, among the hub genes in the top WS-related modules

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