Study of rare genetic variants in TM4SF20, NFXL1, CNTNAP2, and ATP2C2 in Pakistani probands and families with language impairment

• DOI: 10.1016/j.mgene.2021.100966
• Publication Date: 2021-08-27T15:53:25Z
• Authors: Erin M. Andres; HeatherL. Neely; Huma Hafeez; Tahira Yasmin; Farzana Kausar; M. Asim Raza Basra; Muhammad Hashim Raza
• Keywords: Proband; Candidate gene

Language impairment (LI) is highly heritable and aggregates in families. Genetic investigation of LI has revealed many chromosomal regions genes interest, though very few studies have focused on rare variant analysis non-English speaking or non-European samples. We selected four candidate (TM4SF20, NFXL1, CNTNAP2 ATP2C2) strongly suggested for specific language (SLI), a subtype LI, investigated protein coding variants through Sanger sequencing probands with ascertained from Pakistan. The their family members completed speech history questionnaire vocabulary measure, the Peabody Picture Vocabulary Test-fourth edition (PPVT-4), translated to Urdu, national Our study aimed determine significance these SLI segregation novel population high rate consanguinity. In total, we identified 16 (according MAF global gnomAD v2.1.1 database exomes), including eight <0.5 % South Asian population. Most aggregated proband's families, one (c.*9T>C CNTNAP2) co-segregated small (PKSLI-64) another (c.2465C>T proband branch (PKSLI-27). lack complete co-segregation most indicates that while could be involved overall risk other are likely this Future consanguineous families potential expand our understanding gene function related acquisition impairment.