Further evidence of RNU4ATAC variants causing Joubert syndrome with skeletal involvement

Introduction This database includes the VCFs linked with the paper “Further evidence of RNU4ATAC variants causing Joubert syndrome with skeletal involvement”. In this study, we reported the identification of biallelic non-coding variants in RNU4ATAC in three unrelated individuals with a clinical diagnosis of Joubert syndrome (JS), who had remained negative after exome sequencing (ES). Our aim was to investigate the contribution of RNU4ATAC to the JS mutational spectrum and to highlight the relevance of re-analyzing non-coding regions in unsolved cases of JS. Methods ES was performed on DNA from JS patients using standard clinical pipelines. In cases without a definitive molecular diagnosis, we reanalyzed ES for the RNU4ATAC locus, within intron 2 of CLASP1, through direct BAM files inspection. Results (in brief) We identified compound heterozygous RNU4ATAC variants in three individuals from unrelated families. All patients displayed hallmark JS features (including the molar tooth sign) and additional skeletal manifestations. The uploaded VCF files belong to each of these three individuals, supporting the findings discussed in the manuscript.## 引言 本数据库包含与论文《RNU4ATAC变异导致伴骨骼受累的Joubert综合征的进一步证据》相关的变异检测格式文件（VCF）。 本研究报道了在3名临床诊断为Joubert综合征（JS）且经外显子组测序（ES）未检出致病突变的无关个体中，鉴定出RNU4ATAC基因的双等位非编码变异。本研究旨在探究RNU4ATAC在JS突变谱中的贡献，并强调对未明确分子诊断的JS病例重新分析非编码区域的重要性。 ## 方法 本研究采用标准临床测序流程，对JS患者的DNA样本进行外显子组测序。对于未获得明确分子诊断的病例，我们通过直接检查二进制比对映射文件（BAM），针对位于CLASP1内含子2区域内的RNU4ATAC基因座，重新分析其外显子组测序数据。 ## 简要结果 我们在3个无关家系的个体中鉴定出RNU4ATAC基因的复合杂合变异。所有患者均表现出JS的典型特征（包括磨牙征）以及额外的骨骼受累表现。本次上传的VCF文件分别对应这3名个体，为论文中阐述的研究结果提供支撑。