■HMGXB4(另外称为HMG2L1)是一种非组蛋白DNA结合蛋白,包含单个HMG盒结构域。HMGXB4最初被描述在非洲爪鱼中,其中发现它负调节Wnt/β-连环蛋白信号传导途径。
■在这项研究中,我们对一个家庭进行了遗传和临床评估,其中三个受影响的个体患有智力障碍(ID),全球发育迟缓(GDD)和畸形面部特征。对受影响的个体DNA进行全基因组测序(WGS)和Sanger测序以鉴定遗传变异。此外,逆转录-定量聚合酶链反应(RT-qPCR)用于评估家庭中受影响和未受影响个体的基因表达.
■WGS在HMGXB4基因(OMIM604702)的外显子5中鉴定出纯合移码变体c.1193_1196delp.(Lys398Argfs×25),这完全隔离了家族中的疾病表型。此外,RT-qPCR显示,与家族的未受影响的个体相比,受影响的个体中HMGXB4基因表达显著降低。
■当前的研究是第一个将HMGXB4基因中的遗传变异与ID联系起来的证据,GDD,和畸形的面部特征。因此,HMGXB4可能对发育里程碑有重要贡献,并可能是人类神经发育障碍的原因。
UNASSIGNED: HMGXB4 (additionally known as HMG2L1) is a non-histone DNA-binding protein that contains a single HMG-box domain. HMGXB4 was originally described in Xenopus where it was seen to negatively regulate the Wnt/β-catenin signaling pathway.
UNASSIGNED: In this study, we conducted a genetic and clinical evaluation of a single family with three affected individuals suffering from intellectual disability (ID), global developmental delay (GDD) and dysmorphic facial features.Whole genome sequencing (WGS) and Sanger sequencing were performed on the affected individuals\' DNA to identify genetic variations. Additionally, a reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used to assess gene expression in both the affected and unaffected individuals in the family.
UNASSIGNED: WGS identified a homozygous frameshift variant c.1193_1196del p. (Lys398Argfs × 25) in exon 5 of the HMGXB4 gene (OMIM 604702), which completely segregated the disease phenotype in the family. Furthermore, RT-qPCR revealed a substantial decrease in the HMGXB4 gene expression in the affected individuals as compared to the unaffected individuals of the family.
UNASSIGNED: The current study is the first evidence linking a genetic variant in the HMGXB4 gene to ID, GDD, and dysmorphic facial features. Therefore, it is possible that HMGXB4 contributes significantly to developmental milestones and may be responsible for neurodevelopmental disorders in humans.