Bouzid Amal, Belcadhi Malek, Souissi Amal, Chelly Meryam, Frikha Fakher, Gargouri Hela, Bonnet Crystel, Jebali Fida, Loukil Salma, Petit Christine, Masmoudi Saber, Hamoudi Rifat, Ben Said Mariem
Laboratory of Molecular and Cellular Screening Processes, Center of Biotechnology of Sfax, Sfax, Tunisia.
Research Institute for Medical and Health Sciences, University of Sharjah, Sharjah, United Arab Emirates.
Sci Rep. 2025 Jan 2;15(1):367. doi: 10.1038/s41598-024-83115-x.
Developmental language disorder (DLD) is a neurodevelopmental disorder involving impaired language abilities. Its genetic etiology is heterogeneous, involving rare variations in multiple susceptibility loci. However, family-based studies on gene mutations are scarce. We performed whole-exome sequencing (WES) of a first-time-described Tunisian-family with DLD. Analyses of segregation patterns with stringent filtering of the exome data identified disease-causing compound heterozygous variants. In the MRNIP gene, two variants were detected including a synonymous low-frequency variant c.345G > C and a nonsense rare variant c.112G > A predicted pathogenic. In the ABHD14A gene, four variants were identified including a rare missense variant c.689T > G and three splice-site variants c.70-8C > T, c.282-25A > T and c.282-10G > C with low-frequency MAF < 5%. Complementary analyses showed that these variants are predicted pathogenic and the missense variant Leu230Arg significantly affects the stability and structure modelling of the ABHD14A protein. Biological functions and interconnections analyses predicted the potential roles of ABHD14A and MRNIP in neuronal development pathways. These results suggest ABHD14A and MRNIP, as putative candidate genes for DLD susceptibility. Our findings reveal the involvement of novel candidate genes in the genetic etiology of DLD and explore the potential future utility of WES in the diagnosis of such complex disorders.
发育性语言障碍（DLD）是一种涉及语言能力受损的神经发育障碍。其遗传病因具有异质性，涉及多个易感基因座的罕见变异。然而，基于家庭的基因突变研究很少。我们对一个首次描述的患有DLD的突尼斯家庭进行了全外显子组测序（WES）。通过对全外显子数据进行严格筛选的分离模式分析，确定了致病的复合杂合变异。在MRNIP基因中，检测到两个变异，包括一个同义低频变异c.345G＞C和一个预测为致病的无义罕见变异c.112G＞A。在ABHD14A基因中，鉴定出四个变异，包括一个罕见的错义变异c.689T＞G和三个剪接位点变异c.70-8C＞T、c.282-25A＞T和c.282-10G＞C，其低频次要等位基因频率（MAF）＜5%。补充分析表明，这些变异被预测为致病，错义变异Leu230Arg显著影响ABHD14A蛋白的稳定性和结构建模。生物学功能和相互联系分析预测了ABHD14A和MRNIP在神经元发育途径中的潜在作用。这些结果表明ABHD14A和MRNIP作为DLD易感性的假定候选基因。我们的发现揭示了新的候选基因参与DLD的遗传病因，并探索了WES在诊断此类复杂疾病中的潜在未来用途。
