Data set 2 - IEI Exome SNP Discovery

Objectives: Inborn error of immunity (IEI) comprises a broad group of inherited immunological disorders that usually display an overlap in many clinical manifestations challenging their diagnosis. The identification of disease-causing variants comprises the gold-standard approach to ascertain IEI diagnosis. The efforts to increase the availability of clinically relevant genomic data for these disorders constitute an important improvement in the study of rare genetic disorders. This work aims to make available whole-exome sequencing (WES) data of Brazilian patients' suspicion of IEI without a genetic diagnosis. We foresee a broad use of this dataset by the scientific community in order to provide a more accurate diagnosis of IEI disorders. Data description: Twenty singleton unrelated patients treated at four different hospitals in the state of Rio de Janeiro, Brazil were enrolled in our study. Half of the patients were male with mean ages of 9±3, while females were 12±10 years old. The WES was performed in the Illumina NextSeq platform with at least 90% of sequenced bases with a minimum of 30 reads depth. Each sample had an average of 20,274 variants, comprising 116 classified as rare pathogenic or likely pathogenic according to ACMG guidelines. The genotype-phenotype association was impaired by the lack of detailed clinical and laboratory information, besides the unavailability of molecular and functional studies which, comprise the limitations of this study. Overall, the access to clinical exome sequencing data is limited, challenging exploratory analyses and the understanding of genetic mechanisms underlying disorders. Therefore, by making these data available, we aim to increase the number of WES data from Brazilian samples despite contributing to the study of monogenic IEI-disorders.

研究目标：原发性免疫缺陷病（Inborn Error of Immunity, IEI）是一类涵盖范围广泛的遗传性免疫失调疾病，其诸多临床表现存在重叠，这给临床诊断带来了极大挑战。明确致病变异位点是确诊IEI的金标准方法。提升这类疾病相关临床相关基因组数据的可及性，是罕见遗传性疾病研究领域的一项重要进展。本研究旨在公开巴西疑似原发性免疫缺陷病且尚未获得基因诊断的患者的全外显子组测序（Whole-Exome Sequencing, WES）数据。我们期待该数据集能够被科学界广泛使用，以助力原发性免疫缺陷病的精准诊断。数据概况：本研究共纳入20名在巴西里约热内卢州四家不同医院接受诊疗的非亲缘散发性患者。其中男性患者占半数，平均年龄为9±3岁，女性患者平均年龄为12±10岁。测序工作基于Illumina NextSeq平台完成，至少90%的测序碱基覆盖深度不低于30×。每个样本平均存在20274个变异位点，其中依据美国医学遗传学与基因组学学会（American College of Medical Genetics and Genomics, ACMG）指南分类为罕见致病或疑似致病变异的位点共116个。由于缺乏详细的临床与实验室信息，且未开展分子与功能验证研究，本研究在基因型-表型关联分析方面存在局限。总体而言，临床外显子组测序数据的可及性较低，这给探索性分析以及疾病潜在遗传机制的解析带来了挑战。因此，本研究公开这批数据，旨在增加巴西人群来源的全外显子组测序数据储量，同时为单基因原发性免疫缺陷病的研究提供助力。