全球发育迟缓/智力障碍(ID)是一个术语,用于描述由大脑发育异常引起的各种疾病,其特征是认知障碍。通信,行为,或运动技能。在过去的几年里,全外显子组测序(WES)已被证明是一个强大的,健壮,以及在近亲人群中发现候选基因的可扩展方法。在这项研究中,我们从118个中东家庭招募了215例ID患者.对188个个体完成全外显子组测序。完成WES的平均年龄为8.5岁。在32/118个家庭中检测到致病性或可能的致病性变异(27%)。在33/118个家庭(28%)中发现了不确定意义的变体。在32/118(27%)中检测到与ID可能相关的候选基因,总数为64个受影响的个体。这些基因很新颖,以前在一个家庭中报道过,或以不同的遗传方式引起明显不同的表型。这些基因包括:AATK,AP1G2,CAMSAP1,CCDC9B,CNTROB,DNAH14,DNAJB4,DRG1,DTNBP1,EDRF1,EEF1D,EXOC8,EXOSC4,FARSB,FBXO22,FILIP1,INPP4A,P2RX7,PRDM13,PTRHD1,SCN10A,SCYL2、SMG8、SUPV3L1、TACC2、THUMPD1、XPR1、ZFYVE28。在5年的研究中,通过基因匹配数据库,这些基因中的几个现在已经被证实是ID的病因。总之,了解ID的原因将有助于理解生物学机制,为受影响的家庭提供精确的咨询,并协助初级预防。
Global Developmental Delay/Intellectual disability (ID) is the term used to describe various disorders caused by abnormal brain development and characterized by impairments in cognition, communication, behavior, or motor skills. In the past few years, whole-exome sequencing (WES) has been proven to be a powerful, robust, and scalable approach for candidate gene discoveries in consanguineous populations. In this
study, we recruited 215 patients affected with ID from 118 Middle Eastern families. Whole-exome sequencing was completed for 188 individuals. The average age at which WES was completed was 8.5 years. Pathogenic or likely pathogenic variants were detected in 32/118 families (27%). Variants of uncertain significance were seen in 33/118 families (28%). The candidate genes with a possible association with ID were detected in 32/118 (27%) with a total number of 64 affected individuals. These genes are novel, were previously reported in a single family, or cause strikingly different phenotypes with a different mode of inheritance. These genes included: AATK, AP1G2, CAMSAP1, CCDC9B, CNTROB, DNAH14, DNAJB4, DRG1, DTNBP1, EDRF1, EEF1D, EXOC8, EXOSC4, FARSB, FBXO22, FILIP1, INPP4A, P2RX7, PRDM13, PTRHD1, SCN10A, SCYL2, SMG8, SUPV3L1, TACC2, THUMPD1, XPR1, ZFYVE28. During the 5 years of the
study and through gene matching databases, several of these genes have now been confirmed as causative of ID. In conclusion, understanding the causes of ID will help understand biological mechanisms, provide precise counseling for affected families, and aid in primary prevention.