Cruz-Granados Pablo, Bianco-Bortoletto Giselle, Aran Ismael, Rivero de Jesus Victoria, Lopez-Escamez Jose A
Meniere Disease Neuroscience Research Program, Faculty of Medicine & Health, School of Medical Sciences, The Kolling Institute, University of Sydney, Sydney, New South Wales, Australia.
Laboratory of Human Molecular Genetics, Center for Molecular Biology and Genetic Engineering - CBMEG, Programa de Pós Graduação em Ciências Médicas, Faculty of Medical Sciences, State University of Campinas - UNICAMP, Sao Paulo, Brazil.
NPJ Genom Med. 2025 May 20;10(1):42. doi: 10.1038/s41525-025-00503-6.
Menière's disease (MD) is an inner ear disorder characterised by episodes of vertigo, sensorineural hearing loss and tinnitus linked to autoinflammation and/or type 2 immune response. We hypothesise that rare variation in immune response genes could drive the autoinflammatory phenotype in MD. We retrieved differentially expressed genes (DEG) from single-cell RNAseq and epigenomic datasets to search for rare variants in the MD exome (N = 454) and genome (N = 511) sequencing datasets. The variant chr1:10374335 C > T in the KIF1B gene was found in three MD unrelated individuals and was predicted to be likely pathogenic. According to differential transcript usage, transcript ENST00000622724.3 was found in MD samples, but absent in controls. Furthermore, this variant may influence splicing through the generation of exonic enhancers and silencers, potentially changing transcription factor binding at the promoter. These findings support that this KIF1B gene rare variant is associated with the MD autoinflammatory phenotype and may up-regulate its expression in monocytes.
梅尼埃病（MD）是一种内耳疾病，其特征为眩晕发作、感音神经性听力损失和耳鸣，与自身炎症和/或2型免疫反应有关。我们推测免疫反应基因的罕见变异可能驱动MD中的自身炎症表型。我们从单细胞RNA测序和表观基因组数据集中检索差异表达基因（DEG），以在MD外显子组（N = 454）和基因组（N = 511）测序数据集中寻找罕见变异。在三个与MD无关的个体中发现了KIF1B基因中的变异chr1:1037****C>T，并预测其可能具有致病性。根据差异转录本使用情况，在MD样本中发现了转录本ENST00000622724.3，但在对照中不存在。此外，该变异可能通过外显子增强子和沉默子的产生影响剪接，潜在地改变启动子处的转录因子结合。这些发现支持这种KIF1B基因罕见变异与MD自身炎症表型相关，并可能上调其在单核细胞中的表达。
