Abstract
Children affected by Specific Language Impairment (SLI) fail to acquire age appropriate language skills despite adequate intelligence and opportunity. SLI is highly heritable, but the understanding of underlying genetic mechanisms has proved challenging. In this study, we use molecular genetic techniques to investigate an admixed isolated founder population from the Robinson Crusoe Island (Chile), who are affected by a high incidence of SLI, increasing the power to discover contributory genetic factors. We utilize exome sequencing in selected individuals from this population to identify eight coding variants that are of putative significance. We then apply association analyses across the wider population to highlight a single rare coding variant (rs144169475, Minor Allele Frequency of 4.1% in admixed South American populations) in the NFXL1 gene that confers a nonsynonymous change (N150K) and is significantly associated with language impairment in the Robinson Crusoe population (p = 2.04 × 10–4, 8 variants tested). Subsequent sequencing of NFXL1 in 117 UK SLI cases identified four individuals with heterozygous variants predicted to be of functional consequence. We conclude that coding variants within NFXL1 confer an increased risk of SLI within a complex genetic model.
Highlights
The sentence: "The contribution of identified risk variants is subsequently validated by performing targeted sequencing of candidate genes in a UK-based cohort of individuals affected by SLI," should read: "The contribution of identified risk variants is subsequently validated by performing targeted sequencing of a candidate gene in a UK-based cohort of individuals affected by SLI."
The correct contributions are: Conceived and designed the experiments: PV RN AH MAF CG LJ CF GB GCR AOH PFB ERH SLIC HP LCC JAV JBC ZDB SEF DFN Performed the Chilean fieldwork: PV MAF LJ ZDB Performed the genetic experiments: RN AH NHS CG RHR LCC JAV JBC SEF DFN Analyzed the phenotypic data: PV MAF LJ HP ZDB DFN Analyzed the genetic data: RN AH NHS CG RHR LCC JBC SEF DFN Contributed reagents/materials/analysis tools: PV AH MAF CG LJ MME GB GCR AOH PFB ERH SLIC LCC JAV ZDB SEF DFN Wrote the manuscript: PV RN JBC SEF DFN
Summary
The name of the ninth author is incorrect. Maria Magdalena Echeverry should read María Magdalena Echeverry.
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