Pablo Cruz-Granados, Giselle Bianco-Bortoletto, Ismael Aran, Victoria Rivero de Jesus, Jose A Lopez-Escamez
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引用次数: 0
摘要
meni病(MD)是一种内耳疾病,以眩晕、感音神经性听力损失和耳鸣发作为特征,与自身炎症和/或2型免疫反应有关。我们假设免疫反应基因的罕见变异可以驱动MD的自身炎症表型。我们从单细胞RNAseq和表观基因组数据集中检索差异表达基因(DEG),以搜索MD外显子组(N = 454)和基因组(N = 511)测序数据集中的罕见变异。KIF1B基因变异chr1:10374335 C > T在3个与MD无关的个体中被发现,预计可能具有致病性。根据差异转录本使用情况,在MD样本中发现了转录本ENST00000622724.3,但在对照组中没有。此外,这种变异可能通过产生外显子增强子和沉默子来影响剪接,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。
An ultra-rare missense variant in the KIF1B gene linked to autoinflammatory Menière's disease.
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.
NPJ Genomic MedicineBiochemistry, Genetics and Molecular Biology-Molecular Biology
CiteScore
9.40
自引率
1.90%
发文量
67
审稿时长
17 weeks
期刊介绍:
npj Genomic Medicine is an international, peer-reviewed journal dedicated to publishing the most important scientific advances in all aspects of genomics and its application in the practice of medicine.
The journal defines genomic medicine as "diagnosis, prognosis, prevention and/or treatment of disease and disorders of the mind and body, using approaches informed or enabled by knowledge of the genome and the molecules it encodes." Relevant and high-impact papers that encompass studies of individuals, families, or populations are considered for publication. An emphasis will include coupling detailed phenotype and genome sequencing information, both enabled by new technologies and informatics, to delineate the underlying aetiology of disease. Clinical recommendations and/or guidelines of how that data should be used in the clinical management of those patients in the study, and others, are also encouraged.