Exome sequencing in an admixed isolated population indicates NFXL1 variants confer a risk for specific language impairment

Pía Villanueva, Ron Nudel, Alexander Hoischen, María Angélica Fernández, Nuala H Simpson, Christian Gilissen, Rose H Reader, Lillian Jara, María Magdalena Echeverry, Maria Magdalena Echeverry, Clyde Francks, Gillian Baird, Gina Conti-Ramsden, Anne O'Hare, Patrick F Bolton, Elizabeth R Hennessy, Hernán Palomino, Luis Carvajal-Carmona, Joris A Veltman, Jean-Baptiste CazierZulema De Barbieri, Simon E Fisher, Dianne F Newbury, SLI Consortium

Research output: Contribution to journalArticlepeer-review

19 Citations (Scopus)


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.

Original languageEnglish
Article numbere1004925
JournalPLoS Genetics
Issue number3
Publication statusPublished - 17 Mar 2015


Dive into the research topics of 'Exome sequencing in an admixed isolated population indicates NFXL1 variants confer a risk for specific language impairment'. Together they form a unique fingerprint.

Cite this