Abstract：
Intellectual disability (ID) is a condition of significant limitation of cognitive functioning and adaptive behavior, with 50% of etiology attributed to genetic predisposition. We recruited two consanguineous Pakistani families manifesting severe ID and developmental delay. The probands were subjected to whole exome sequencing (WES) and variants were further prioritized based on population frequency, predicted pathogenicity and functional relevance. The WES data analysis identified homozygous pathogenic variants in genes MBOAT7 and TRAPPC9. The pathogenicity of the variants was supported by co-segregation analysis and in silico tool. The findings of this study expand mutation spectrum and provide additional evidence to the role of MBOAT7 and TRAPPC9 in causation of ID.
摘要：
智力残疾（ID）是认知功能和适应性行为的显着限制的条件，50%的病因归因于遗传易感性。我们招募了两个有严重ID和发育迟缓的近亲巴基斯坦家庭。先证者进行全外显子组测序（WES），并根据种群频率进一步确定变体的优先级。预测致病性和功能相关性。WES数据分析鉴定了基因MBOAT7和TRAPPC9中的纯合致病变体。变体的致病性得到共分离分析和硅片工具的支持。这项研究的发现扩展了突变谱，并为MBOAT7和TRAPPC9在ID的因果关系中的作用提供了额外的证据。
