Andres Erin M, Earnest Kathleen Kelsey, Xuan Hao, Zhong Cuncong, Rice Mabel L, Raza Muhammad Hashim
Thompson Center for Autism and Neurodevelopment, University of Missouri, Columbia, MO 65201, USA.
Language Acquisition Studies Lab, University of Kansas, Lawrence, KS 66045, USA.
Children (Basel). 2023 Jun 28;10(7):1119. doi: 10.3390/children10071119.
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 ( = 74 total) and follow-up Sanger sequencing in additional unrelated probands ( = 146). We prioritized rare exonic variants shared by individuals with low TEGI performance ( = 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 (, , , , , and ), and two genes previously reported for overall language ability ( and ). We specifically suggest , a protocadherin gene, and 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.
患有特定语言障碍（SLI）的个体尽管具有平均水平的非语言智力且其他方面发育正常，但在语言习得方面仍存在困难。一种关于SLI的观点聚焦于语法习得延迟。本研究旨在检测与英语儿童语法评估（早期语法损伤测试，TEGI）表现相关的新型罕见基因变异。选择TEGI是因其敏感性和特异性、一直以来较高的遗传度估计值，以及除一项分子遗传学研究外其他研究均未涉及。我们对8个患有SLI的家庭（共74人）进行了全外显子组测序（WES），并对另外146名无亲缘关系的先证者进行了后续的桑格测序。我们在两种筛选流程下，优先考虑至少两个家庭中TEGI表现较低的个体（共34人）共有的罕见外显子变异：（1）新型变异和（2）先前报道的候选基因。在6个新基因（、、、、、和）以及先前报道与整体语言能力相关的2个基因（和）上观察到了候选变异。我们特别指出，原钙黏蛋白基因和对核糖体合成至关重要，因为它们是SLI研究的重要靶点。与TEGI表现相关的拟SLI候选基因强调了精确表型分型和基于家系的遗传学研究的实用性。
