Department of Gynecology and Obstetrics, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400000, China.
Center for Clinical Genetics and Genomics, DIAN Diagnostics, Hangzhou, 310058, Zhejiang, China.
J Hum Genet. 2024 Aug;69(8):391-400. doi: 10.1038/s10038-024-01255-4. Epub 2024 May 13.
F-box protein 11 (FBXO11) is a member of F-Box protein family, which has recently been proved to be associated with intellectual developmental disorder with dysmorphic facies and behavioral abnormalities (IDDFBA, OMIM: 618089). In this study, 12 intellectual disability individuals from 5 Chinese ID families were collected, and whole exome sequencing (WES), sanger sequencing, and RNA sequencing (RNA-seq) were conducted. Almost all the affected individuals presented with mild to severe intellectual disability (12/12), global developmental delay (10/12), speech and language development delay (8/12) associated with a range of alternate features including increased body weight (7/12), short stature (6/12), seizures (3/12), reduced visual acuity (4/12), hypotonia (1/12), and auditory hallucinations and hallucinations (1/12). Distinguishingly, malformation was not observed in all the affected individuals. WES analysis showed 5 novel FBXO11 variants, which include an inframe deletion variant, a missense variant, two frameshift variants, and a partial deletion of FBXO11 (exon 22-23). RNA-seq indicated that exon 22-23 deletion of FBXO11 results in a new mRNA structure. Conservation and protein structure prediction demonstrated deleterious effect of these variants. The DEGs analysis revealed 148 differentially expressed genes shared among 6 affected individuals, which were mainly associated with genes of muscle and immune system. Our research is the first report of FBXO11-associated IDDFBA in Chinese individuals, which expands the genetic and clinical spectrum of this newly identified NDD/ID syndrome.
F-box 蛋白 11（FBXO11）是 F-Box 蛋白家族的一员，最近已被证实与伴有畸形面容和行为异常的智力发育障碍（IDDFBA，OMIM：618089）有关。在这项研究中，收集了来自 5 个中国 ID 家系的 12 名智力障碍个体，进行了全外显子组测序（WES）、Sanger 测序和 RNA 测序（RNA-seq）。几乎所有受影响的个体都表现出轻度至重度智力障碍（12/12）、全面发育迟缓（10/12）、言语和语言发育迟缓（8/12），并伴有一系列其他特征，包括体重增加（7/12）、身材矮小（6/12）、癫痫发作（3/12）、视力下降（4/12）、张力减退（1/12）和听觉幻觉和幻觉（1/12）。值得注意的是，所有受影响的个体均未观察到畸形。WES 分析显示 5 种新型 FBXO11 变异体，包括移码缺失变异体、错义变异体、2 种移码变异体和 FBXO11 的部分缺失（exon22-23）。RNA-seq 表明 FBXO11 的 exon22-23 缺失导致新的 mRNA 结构。保守性和蛋白质结构预测表明这些变异体具有有害影响。DEGs 分析显示，在 6 名受影响的个体中共有 148 个差异表达基因，这些基因主要与肌肉和免疫系统的基因有关。我们的研究是中国人群中首次报道的 FBXO11 相关 IDDFBA，扩展了这一新确定的 NDD/ID 综合征的遗传和临床谱。
