Delving into the Genetic Causes of Language Impairment in a Case of Partial Deletion of NRXN1 .

INTRODUCTION: Copy-number variations (CNVs) impacting on small DNA stretches and associated with language deficits provide a unique window to the role played by specific genes in language function.

METHODS: We report in detail on the cognitive, language, and genetic features of a girl bearing a small deletion (0.186 Mb) in the 2p16.3 region, arr[hg19] 2p16.3(50761778_50947729)×1, affecting exons 3-7 of NRXN1 , a neurexin-coding gene previously related to schizophrenia, autism (ASD), attention deficit hyperactivity disorder (ADHD), mood disorder, and intellectual disability (ID).

RESULTS: 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). Microarray analyses point to the dysregulation of several genes important for language function in the girl compared to her healthy parents.

DISCUSSION: Although some basic cognitive deficit - such as the impairment of executive function - might contribute to the language problems exhibited by the proband, molecular evidence suggests that they might result, to a great extent, from the abnormal expression of genes directly related to language.