Engvall Marie, Karlsson Ylva, Kuchinskaya Ekaterina, Jörnegren Åsa, Mathot Lucy, Pandzic Tatjana, Palle Josefine, Ljungström Viktor, Cavelier Lucia, Hellström Lindberg Eva, Cammenga Jörg, Baliakas Panagiotis
Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
Department of Clinical Pathology and Clinical Genetics, and Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
Leuk Lymphoma. 2022 Oct;63(10):2311-2320. doi: 10.1080/10428194.2022.2067997. Epub 2022 May 9.
Germline pathogenic variants in are associated with familial platelet disorder with predisposition to myeloid malignancies (FPD/MM) with intragenic deletions in accounting for almost 7% of all reported variants. We present two new pedigrees with FPD/MM carrying two different germline intragenic deletions. The aforementioned deletions encompass exons 1-2 and 9-10 respectively, with the exon 9-10 deletion being previously unreported. RNA sequencing of patients carrying the exon 9-10 deletion revealed a fusion with resulting in a change in the 3' sequence of . Expression analysis of the transcript isoform demonstrated altered ratios in carriers from both families compared to controls. Our data provide evidence on the impact of intragenic deletions on transcript isoform expression and highlight the importance of routinely performing copy number variant analysis in patients with suspected MM with germline predisposition.
中的种系致病变异与易患髓系恶性肿瘤的家族性血小板疾病（FPD/MM）相关，其中的基因内缺失占所有报告变异的近7%。我们展示了两个患有FPD/MM的新谱系，它们携带两种不同的种系基因内缺失。上述缺失分别涵盖外显子1-2和9-10，其中外显子9-10缺失此前未被报道。对携带外显子9-10缺失的患者进行RNA测序，发现与形成融合，导致的3'序列发生改变。对转录本异构体的表达分析表明，与对照组相比，两个家族携带者中的比例均发生了改变。我们的数据提供了基因内缺失对转录本异构体表达影响的证据，并强调了对疑似有胚系易感性的MM患者常规进行拷贝数变异分析的重要性。
