Delving into the genetic causes of language impairment in people with partial deletions of NRXN1

Abstract

Copy-number variations (CNVs) impacting on small DNA stretches and that are associated to language deficits provide a unique window to the role played by specific genes in language function. We report in detail on the cognitive and language features of a girl bearing a small deletion (0,186 Mb) in the 2p16.3 region (arr[hg19] 2p16.3(50761778-50947729)x1), affecting to exons 3-7 of NRXN1, a neurexin-coding gene previously related to schizophrenia (SZ), autism (ASD), attention deficit hyperactivity disorder (ADHD), mood disorder, and intellectual disability (ID). The proband exhibits many of the features commonly found in subjects with deletions of NRXN1, like ASD-like traits (including ritualized behaviors, disordered sensory aspects, social disturbances and impaired theory of mind), ADHD symptoms, moderate ID, and impaired speech and language. Regarding this latter aspect, we observed altered speech production, underdeveloped phonological awareness, minimal syntax, serious shortage of active vocabulary, impaired receptive language, and inappropriate pragmatic behavior (including lack of metapragmatic awareness and communicative use of gaze). Although these problems might arise from some basic cognitive deficit, such as the impairment of executive function, we provide evidence that several genes important for language function are dysregulated in the proband compared to their healthy parents.