A specific cognitive deficit within semantic cognition across a multi-generational family

Abstract

We report a study of eight members of a single family (aged 8–72 years), who all show a specific deficit in linking semantic knowledge to language. All affected members of the family had high levels of overall intelligence; however, they had profound difficulties in prose and sentence recall, listening comprehension and naming. The behavioural deficit was remarkably consistent across affected family members. Structural neuroimaging data revealed grey matter abnormalities in the left infero-temporal cortex and fusiform gyri: brain areas that have been associated with integrative semantics. This family demonstrates, to our knowledge, the first example of a heritable, highly specific abnormality affecting the interface between language and cognition in humans and has important implications for our understanding of the genetic basis of cognition.

Understanding Language from a Genomic Perspective

“…Sequencing of parent-child trios in which the child has a severe sporadic language disorder may identify high-penetrance de novo variants. Extended families have also been described segregating potentially monogenic forms of language-related disorder (17,120). NGS in such families could uncover etiological variants more effectively than earlier methods that depend only on linkage screening.…”

Speech and Language: Translating the Genome

“…Complementary to studying common variation, identification of novel genetic contributions to speech/language phenotypes will greatly benefit from increased use of NGS platforms to discover rare variants with large effects. One strategy is to apply whole-exome or wholegenome sequencing in large families showing potential monogenic transmission of a languagerelated disorder [93,94], although there are no guarantees that such approaches will pinpoint a single causal variant in the family being studied. [ 4 2 5 _ T D $ D I F F ] Useful insights may also emerge from GWAS and/or NGS in geographical isolates with dramatically increased prevalence of language disorders, as shown by studies of SLI implicating variants in SETBP1 and MEF2-regulated genes in a remote cluster of Russian villages [95], and a variant of NFXL1 in a founder population from Robinson Crusoe Island (Chile) [96].…”

Receptive vocabulary and semantic knowledge in children with SLI and children with Down syndrome

“…Although the neuroanatomical basis for impaired semantic cognition in DS is poorly specified, these data contribute to emerging evidence of specific impairments to semantic cognition to be identified in developmental populations (Briscoe, Chilvers, Baldeweg, and Skuse, 2012;Nation and Snowling, 1999).…”