Microdeletions of ELP4 Are Associated with Language Impairment, Autism Spectrum Disorder, and Mental Retardation

Research output: Contribution to journalJournal articleResearchpeer-review

Laura Addis, Joo Wook Ahn, Richard Dobson, Abhishek Dixit, Caroline M Ogilvie, Dalila Pinto, Andrea K Vaags, Hilary Coon, Pauline Chaste, Scott Wilson, Jeremy R Parr, Joris Andrieux, Bruno Lenne, Zeynep Tumer, Vincenzo Leuzzi, Kristina Aubell, Hannele Koillinen, Sarah Curran, Christian R Marshall, Stephen W Scherer & 3 others Lisa J Strug, David A Collier, Deb K Pal

Copy-number variations (CNVs) are important in the aetiology of neurodevelopmental disorders and show broad phenotypic manifestations. We compared the presence of small CNVs disrupting the ELP4-PAX6 locus in 4,092 UK individuals with a range of neurodevelopmental conditions, clinically referred for array comparative genomic hybridization, with WTCCC controls (n = 4,783). The phenotypic analysis was then extended using the DECIPHER database. We followed up association using an autism patient cohort (n = 3,143) compared with six additional control groups (n = 6,469). In the clinical discovery series, we identified eight cases with ELP4 deletions, and one with a partial duplication of ELP4 and PAX6. These cases were referred for neurological phenotypes including language impairment, developmental delay, autism, and epilepsy. Six further cases with a primary diagnosis of autism spectrum disorder (ASD) and similar secondary phenotypes were identified with ELP4 deletions, as well as another six (out of nine) with neurodevelopmental phenotypes from DECIPHER. CNVs at ELP4 were only present in 1/11,252 controls. We found a significant excess of CNVs in discovery cases compared with controls, P = 7.5 × 10(-3) , as well as for autism, P = 2.7 × 10(-3) . Our results suggest that ELP4 deletions are highly likely to be pathogenic, predisposing to a range of neurodevelopmental phenotypes from ASD to language impairment and epilepsy.

Original languageEnglish
JournalHuman Mutation
Volume36
Issue number9
Pages (from-to)842-50
Number of pages9
ISSN1059-7794
DOIs
Publication statusPublished - Sep 2015

    Research areas

  • Adolescent, Adult, Autism Spectrum Disorder, Case-Control Studies, Child, Child, Preschool, Comparative Genomic Hybridization, DNA Copy Number Variations, Databases, Genetic, Datasets as Topic, Female, Genetic Association Studies, Humans, Infant, Inheritance Patterns, Intellectual Disability, Language Disorders, Male, Nerve Tissue Proteins, Phenotype, Sequence Deletion, Young Adult

ID: 162215497