Copy Number Variation Screen Identifies a Rare De Novo Deletion at Chromosome 15q13.1-13.3 in a Child with Language Impairment.

Kerry A Pettigrew,Silvia Paracchini,Anahita Sharma,Paul Thompson,Ruth Leavett,Dianne F Newbury,Margaret J Snowling,Marianna E Hayiou-Thomas,Angela Martinelli,Charles Hulme,Nuala H Simpson,Emily Reeves,Bert De Smedt

doi:10.1371/journal.pone.0134997

Abstract

A significant proportion of children (up to 7% in the UK) present with pronounced language difficulties that cannot be explained by obvious causes like other neurological and medical conditions. A substantial genetic component is predicted to underlie such language problems. Copy number variants (CNVs) have been implicated in neurodevelopmental and psychiatric conditions, such as autism and schizophrenia, but it is not fully established to what extent they might contribute to language disorders. We conducted a CNV screen in a longitudinal cohort of young children with language-related difficulties (n = 85), focusing on single events at candidate loci. We detected a de novo deletion on chromosome 15q13.1–13.3. The adjacent 15q11-13.1 locus is disrupted in Prader-Willi and Angelman syndromes, while disruptions across the breakpoints (BP1-BP6) have previously been implicated in different neurodevelopmental phenotypes including autism, intellectual disability (ID), seizures and developmental delay (DD). This is the first report of a deletion at BP3-BP5 being linked to a deficit confined to language impairment, in the absence of ID, expanding the range of phenotypes that implicate the chromosome 15q13 locus.

Highlights

3–7% of pre-school English-speaking children have pronounced language impairment (LI) [1], which cannot be accounted for by intellectual, sensory or physical impairment, or by poor educational opportunities [2,3]
A full list of all consistent highconfidence Copy number variants (CNVs) identified in probands and siblings has been submitted to the DGV archive
We conducted a CNV screen in 85 children recruited in a longitudinal cohort designed to study the development of children with impaired language and/or a family history of dyslexia [29,30]

Summary

Introduction

3–7% of pre-school English-speaking children have pronounced language impairment (LI) [1], which cannot be accounted for by intellectual, sensory or physical impairment, or by poor educational opportunities [2,3]. LI is often the manifestation of other profound deficits or conditions. It often co-occurs with learning difficulties, such as reading problems (or dyslexia). De Novo 15q13.1-13.3 Deletion and Language Impairment. Support to the analysis was provided by the St Andrews Bioinformatics Unit funded by the Wellcome Trust [097831/Z/11/Z].

Methods

Results

Conclusion