Biology subjects

Jimenez-Romero, M. S.

Publications and source records attributed to Jimenez-Romero, M. S..

4 recordsLinked to original sources

bioRxiv2020

Language impairment with a partial duplication of DOCK8

Copy-number variations of the distal region of the short arm of chromosome 9 are associated with learning disabilities and behavioral disturbances. Deletions of the 9p are more frequent than duplications. We report in detail on the cognitive and language features of a child with a duplication in the 9p24.3 region (arr[hg19] 9p24.3(266,045-459,076)x3). He exhibits marked expressive and receptive problems, which affect to both structural aspects of language (notably, inflectional morphology, complex syntax, and sentence semantics), and to functional aspects (pragmatics). These problems might result from a severe underlying deficit in working memory. Regarding the molecular causes of the observed symptoms, they might result from the altered expression of selected genes involved in procedural learning, particularly, some of components of the SLIT/ROBO/FOXP2 network, strongly related to the development and evolution of language. Dysregulation of specific components of this network can result in turn from an altered interaction between DOCK8, affected by the microduplication in 9p24.3 borne by our proband, and CDC42, acting as the hub component of the network encompassing language-related genes. Still, some genes found strongly upregulated in the subject and not related to these genes, particularly NRCAM, can contribute to the observed problems in the language domain, as well as to specific features of the proband, particularly, his impulsivity.

neuroscience↗

bioRxiv2020

Language impairment with a microduplication in 1q42.3q43

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 features 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). Standardized tests as well as the analysis of her language use in natural settings suggest that the probands 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. In silico analyses (literature mining, network analysis) and in vitro analyses (microarray) point to several genes as potential candidates for the observed deficits in the language domain. 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 their healthy parents, and CNTNAP3, found strongly upregulated.

neuroscience↗

bioRxiv2017

Language and cognitive impairment associated to a novel p.Cys63Arg change in the MED13L gene

Mutations of the MED13L gene, which encodes a subunit of a transcriptional regulatory complex, result in a complex phenotype entailing physical and cognitive anomalies. Deep language impairment has been reported, mostly in patients with CNV. Case presentation. We report on a child who presents with a non-synonymous change p.Cys63Arg in MED13L (Chr12:116675396A>G, GRCh37) and who exhibits profound language impairment in the expressive domain, cognitive delay, behavioral disturbances, and some autistic features. Conclusions. Because of the brain areas in which MED13L is expressed and because of the functional links between MED13L and the products of some candidate genes for language disorders, the probands linguistic phenotype may result from changes in a functional network important for language development.

neuroscience↗

bioRxiv2016

Variable penetrance of the 15q11.2 BP1-BP2 microduplication in a family with cognitive and language impairment

The 15q11.2 BP1-BP2 region is found duplicated or deleted in people with cognitive, language, and behavioral impairment. Case presentation. We report on a family (the father and three male twin siblings) who presents with a duplication of the 15q11.2 BP1-BP2 region and a variable phenotype: whereas the father and the fraternal twin are normal carriers, the monozygotic twins exhibit severe language and cognitive delay and behavioral disturbances. The genes located within the duplicated region are involved in brain development and function, and some of them are related to language processing. Conclusions. The probands phenotype may result from changes in the expression level of some of these genes important for cognitive development.

neuroscience↗