Trizuljak Jakub, Petruchová Terezie, Blaháková Ivona, Vrzalová Zuzana, Hořínová Věra, Doubková Martina, Michalka Jozef, Mayer Jiří, Pospíšilová Šárka, Doubek Michael
Faculty of Medicine, Masaryk University, Brno, Czech Republic.
Department of Internal Medicine, Hematology and Oncology, University Hospital Brno, Brno, Czech Republic.
Mol Syndromol. 2020 Jun;11(2):73-82. doi: 10.1159/000507006. Epub 2020 Mar 21.
Bloom syndrome is an autosomal recessive disorder characterized by prenatal and postnatal growth deficiency, photosensitive skin changes, immune deficiency, insulin resistance, and a greatly increased risk of early-onset cancer and development of multiple malignancies. Loss-of-function variants of the gene, which codes for a RecQ helicase, cause Bloom syndrome. We report a consanguineous family, with 2 siblings showing clinical signs of suspected chromosome breakage disorder. One of them developed recurrent malignant lymphoma during lifetime. We performed next-generation sequencing analysis, focusing on cancer predisposition syndromes. We identified a homozygous pathogenic nonsense variant c.1642C>T (p.Gln548*) in the gene in the proband, associated with Bloom syndrome. Sanger sequencing validated the presence of a homozygous pathogenic variant in the proband and also in the brother with short stature. In this article, we will focus on the clinical presentation of the syndrome in this particular family as well as the characteristics of malignancies found in the proband.
布卢姆综合征是一种常染色体隐性疾病，其特征为产前和产后生长发育迟缓、光敏性皮肤改变、免疫缺陷、胰岛素抵抗，以及早发性癌症和多种恶性肿瘤发生风险大幅增加。编码RecQ解旋酶的基因功能丧失变异导致布卢姆综合征。我们报告了一个近亲结婚家庭，有2名兄弟姐妹表现出疑似染色体断裂疾病的临床症状。其中一人在一生中患复发性恶性淋巴瘤。我们进行了二代测序分析，重点关注癌症易感综合征。我们在先证者中鉴定出该基因的一个纯合致病性无义变异c.1642C>T（p.Gln548*），与布卢姆综合征相关。桑格测序验证了先证者以及身材矮小的兄弟中存在纯合致病性变异。在本文中，我们将重点关注该特定家庭中该综合征的临床表现以及先证者中发现的恶性肿瘤特征。
