Innovative Family-Based Genetically Informed Series of Analyses of Whole-Exome Data Supports Likely Inheritance for Grammar in Children with Specific Language Impairment

Bibliographic Data

ID15713499
AuthorsErin M Andres (0000-0002-3331-6728, University of Missouri), Kathleen Kelsey Earnest (0000-0002-6911-4335, University of Kansas), Hao Xuan (University of Kansas), Cuncong Zhong (0000-0002-8777-082X, University of Kansas), Mabel L Rice (0000-0002-8150-5523, University of Kansas), Muhammad Hashim Raza (0000-0002-7027-5195, University of Kansas, corresponding author)
Year2023
Volume10
Issue7
Pages1119-1119
Publication date2023-06-28
Open AccessYes
TypeARTICLE
VenueChildren (JOURNAL)
Journal identifiersISSN: 2227-9067 • E-ISSN: 2227-9067
PublisherMultidisciplinary Digital Publishing Institute (PUBLISHER • CH)
DOI10.3390/children10071119
PMID37508616
OpenAlexW4382584475
LanguageEN
References cited67

Individuals with specific language impairment (SLI) struggle with language acquisition despite average non-verbal intelligence and otherwise typical development. One SLI account focuses on grammar acquisition delay. The current study aimed to detect novel rare genetic variants associated with performance on a grammar assessment, the Test of Early Grammatical Impairment (TEGI), in English-speaking children. The TEGI was selected due to its sensitivity and specificity, consistently high heritability estimates, and its absence from all but one molecular genetic study. We performed whole exome sequencing (WES) in eight families with SLI ( n = 74 total) and follow-up Sanger sequencing in additional unrelated probands ( n = 146). We prioritized rare exonic variants shared by individuals with low TEGI performance ( n = 34) from at least two families under two filtering workflows: (1) novel and (2) previously reported candidate genes. Candidate variants were observed on six new genes ( PDHA2 , PCDHB3 , FURIN , NOL6 , IQGAP3 , and BAHCC1 ), and two genes previously reported for overall language ability ( GLI3 and FLNB ). We specifically suggest PCDHB3 , a protocadherin gene, and NOL6 are critical for ribosome synthesis, as they are important targets of SLI investigation. The proposed SLI candidate genes associated with TEGI performance emphasize the utility of precise phenotyping and family-based genetic study

Biology · Candidate gene · Developmental psychology · Exome sequencing · Gene · Mutation · Sanger sequencing · Specific language impairment · Genetics and Neurodevelopmental Disorders · Language Development and Disorders · Psychology · RNA and protein synthesis mechanisms · Genetics

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