Deletions and duplications of the distal region of the long arm of chromosome 1 are associated with brain abnormalities and developmental delay. Because duplications are less frequent than deletions, no detailed account of the cognitive profile of the affected people is available, particularly, regarding their language (dis)abilities. In this paper we report on the cognitive and language capacities of a girl with one of the smallest interstitial duplications ever described in this region, affecting to 1q42.3q43 (arr[hg19] 1q42.3q43(235,963,632-236,972,276)x3), and advance potential candidate genes for the observed deficits. The proband's speech is severely impaired, exhibiting dysarthric-like features, with speech problems also resulting from a phonological deficit boiling down to a verbal auditory memory deficit. Lexical and grammatical knowledge are also impaired, impacting negatively on both expressive and receptive abilities, seemingly as a consequence of the phonological deficit. Still, her pragmatic abilities seem to be significantly spared, granting her a good command on the principles governing conversational exchanges. Genetic analyses point to several genes of interest. These include one gene within the duplicated region (LYST), one predicted functional partner (CMIP), and three genes outside the 1q42.3q43 region, which are all highly expressed in the cerebellum: DDIT4 and SLC29A1, found strongly downregulated in the proband compared to her healthy parents, and CNTNAP3, found strongly upregulated. The genes highlighted in the paper emerge as potential candidates for the phonological and speech deficits exhibited by the proband and ultimately, for her problems with language.
Keywords: 1q distal duplications; differentially-expressed genes; language deficits; speech problems.