Whole-exome sequencing variant prioritization in individuals with tense and agreement marking deficit— a clinical marker of specific language impairment

Specific language impairment (SLI) has been studied at the genetic level for over 25 years, with varied assessments of language ability defining the SLI phenotype across studies. In the current study, the SLI phenotype is defined by performance on a sensitive and specific measure of grammar impairment, the Test of Early Grammatical Impairment (TEGI). The TEGI is known for its ability to distinguish children with and without SLI at a young age (normed for children ages 3;0 to 8;11 years) and is based in linguistic theory of tense and agreement marking acquisition in English-speaking children. Individuals with SLI, as measured by performance on the TEGI (n = 34), from eight families (total n = 74) were targeted for prioritization of rare exonic variants from whole-exome sequencing (WES) output under two filtering workflows (one targeting previous genetic reports). The current study uniquely combines family-specific filtering of the WES variants and cross-referencing of the familywise variant lists to suggest six new genes (PDHA2, PCDHB3, FURIN, NOL6, IQGAP3, and BAHCC1) possibly involved in SLI, and evidence supporting two genes previously reported as genes likely contributing to overall language ability (GLI3 and FLNB). Importantly, the results show selective prioritization of genes associated with low performance on the TEGI and underline the importance of family-based genetic study. Evidence at the family-level, from bioinformatic prediction tools, and brain expression databases indicate the prioritized genes are strong targets for future functional investigation to better understand their possible role in language acquisition and impairment.

Grantor dc:publisher

University of Kansas

Year dc:date.issued

2022

Author dc:creator

• Andres, Erin Marie

Advisors dc:contributor.advisor

• Rice, Mabel L
• Raza, Muhammed Hashim

• Genetics
• Language
• family-based
• grammar impairment
• specific language impairment
• whole-exome sequencing

Statement dc:rights

• Copyright held by the author.

Language dc:language.iso

en

Dc Identifier Other

http://dissertations.umi.com/ku:18400

OAI identifier oai:identifier

oai:kuscholarworks.ku.edu:1808/35638