Genome Institute of Singapore (GIS), Agency for Science, Technology and Research (A*STAR), Singapore 138672, Singapore.
Department of Surgery, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119228, Singapore.
Int J Mol Sci. 2024 Aug 21;25(16):9058. doi: 10.3390/ijms25169058.
Idiopathic granulomatous mastitis (IGM) is a rare condition characterised by chronic inflammation and granuloma formation in the breast. The aetiology of IGM is unclear. By focusing on the protein-coding regions of the genome, where most disease-related mutations often occur, whole-exome sequencing (WES) is a powerful approach for investigating rare and complex conditions, like IGM. We report WES results on paired blood and tissue samples from eight IGM patients. Samples were processed using standard genomic protocols. Somatic variants were called with two analytical pipelines: nf-core/sarek with and GATK4 with . Our WES study of eight patients did not find evidence supporting a clear genetic component. The discrepancies between variant calling algorithms, along with the considerable genetic heterogeneity observed amongst the eight IGM cases, indicate that common genetic drivers are not readily identifiable. With only three genes, , , and , recurrently altering in multiple cases, the genetic basis of IGM remains uncertain. The absence of validation for somatic variants by Sanger sequencing raises further questions about the role of genetic mutations in the disease. Other potential contributors to the disease should be explored.
特发性肉芽肿性乳腺炎(IGM)是一种罕见的疾病,其特征是乳房内慢性炎症和肉芽肿形成。IGM 的病因尚不清楚。全外显子组测序(WES)是一种强大的方法,可以研究罕见和复杂的疾病,如 IGM,重点关注基因组的蛋白编码区域,大多数与疾病相关的突变通常发生在该区域。我们报告了 8 名 IGM 患者配对的血液和组织样本的 WES 结果。样品采用标准基因组学方案进行处理。体细胞变异使用两种分析管道进行调用:nf-core/sarek with 和 GATK4 with 。我们对 8 名患者的 WES 研究没有发现支持明确遗传成分的证据。变异调用算法之间的差异,以及在 8 个 IGM 病例中观察到的相当大的遗传异质性,表明常见的遗传驱动因素不容易识别。只有三个基因、和在多个病例中反复改变,IGM 的遗传基础仍然不确定。Sanger 测序未能对体细胞变异进行验证,这进一步引发了遗传突变在疾病中的作用的问题。应该探索其他潜在的疾病诱因。