Gönenc Ipek Ilgin, Elcioglu Nursel H, Martinez Grijalva Carolina, Aras Seda, Großmann Nadine, Praulich Inka, Altmüller Janine, Kaulfuß Silke, Li Yun, Nürnberg Peter, Burfeind Peter, Yigit Gökhan, Wollnik Bernd
Institute of Human Genetics, University Medical Center Göttingen, Göttingen, Germany.
Department of Pediatric Genetics, Marmara University Medical School, Istanbul, Turkey.
Clin Genet. 2022 May;101(5-6):559-564. doi: 10.1111/cge.14125. Epub 2022 Mar 11.
Bloom syndrome (BS) is an autosomal recessive disorder with characteristic clinical features of primary microcephaly, growth deficiency, cancer predisposition, and immunodeficiency. Here, we report the clinical and molecular findings of eight patients from six families diagnosed with BS. We identified causative pathogenic variants in all families including three different variants in BLM and one variant in RMI1. The homozygous c.581_582delTT;p.Phe194* and c.3164G>C;p.Cys1055Ser variants in BLM have already been reported in BS patients, while the c.572_573delGA;p.Arg191Lysfs4 variant is novel. Additionally, we present the detailed clinical characteristics of two cases with BS in which we previously identified the biallelic loss-of-function variant c.1255_1259delAAGAA;p.Lys419Leufs5 in RMI1. All BS patients had primary microcephaly, intrauterine growth delay, and short stature, presenting the phenotypic hallmarks of BS. However, skin lesions and upper airway infections were observed only in some of the patients. Overall, patients with pathogenic BLM variants had a more severe BS phenotype compared to patients carrying the pathogenic variants in RMI1, especially in terms of immunodeficiency, which should be considered as one of the most important phenotypic characteristics of BS.
布卢姆综合征（BS）是一种常染色体隐性疾病，具有原发性小头畸形、生长发育迟缓、癌症易感性和免疫缺陷等特征性临床症状。在此，我们报告了来自六个家庭的八名被诊断为BS的患者的临床和分子学研究结果。我们在所有家庭中都鉴定出了致病的致病变异，包括BLM基因中的三种不同变异和RMI1基因中的一种变异。BLM基因中的纯合子c.581_582delTT;p.Phe194和c.3164G>C;p.Cys1055Ser变异已在BS患者中报道过，而c.572_573delGA;p.Arg191Lysfs4变异是新发现的。此外，我们还展示了两例BS患者的详细临床特征，我们之前在这两例患者中鉴定出了RMI1基因的双等位基因功能丧失变异c.1255_1259delAAGAA;p.Lys419Leufs*5。所有BS患者都有原发性小头畸形、宫内生长迟缓以及身材矮小，呈现出BS的典型表型特征。然而，仅在部分患者中观察到了皮肤病变和上呼吸道感染。总体而言，与携带RMI1基因致病变异的患者相比，携带BLM基因致病变异的患者BS表型更为严重，尤其是在免疫缺陷方面，这应被视为BS最重要的表型特征之一。
