Partial Jacobsen syndrome phenotype in a patient with a de novo frameshift mutation in the ETS1 transcription factor.
Partial Jacobsen syndrome phenotype in a patient with a de novo frameshift mutation in the ETS1 transcription factor.
复制标题
ETS1 转录因子发生从头移码突变的患者的部分雅各布森综合征表型。
DOI：
10.1101/mcs.a004010
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发表时间：
2019
影响因子：
1.8
通讯作者：
Grossfeld,Paul
中科院分区：
文献类型：
--
作者：
Tootleman,Eva;Malamut,Barbara;Akshoomoff,Natacha;Mattson,SarahN;Hoffman,HalM;Jones,MarilynC;Printz,Beth;Shiryaev,SergeyA;Grossfeld,Paul
雅各布森综合征 (OMIM #147791) 是一种罕见的连续基因疾病，由远端 11q 缺失引起。临床表型多种多样，可能包括畸形特征、不同程度的智力障碍、行为问题（包括自闭症和注意力缺陷多动障碍）、先天性心脏缺陷、结构性肾脏缺陷、泌尿生殖系统问题、免疫缺陷以及由于血小板生成和功能受损而导致的出血性疾病。先前结合人类和动物系统的研究表明，11q 远端的几个致病基因与雅各布森综合征表型有关。 ETS1 基因与导致先天性心脏缺陷、结构性肾脏缺陷和免疫缺陷有关。我们对一名先天性心脏病患者进行了全面的表型分析，该患者之前发现 ETS1 存在从头移码突变，导致该蛋白的 DNA 结合域丢失。我们的结果表明，Ets1 缺失会导致“部分雅各布森综合征表型”，包括先天性心脏病、面部畸形、智力障碍和注意力缺陷多动障碍。
Jacobsen syndrome (OMIM #147791) is a rare contiguous gene disorder caused by deletions in distal 11q. The clinical phenotype is variable and can include dysmorphic features, varying degrees of intellectual disability, behavioral problems including autism and attention deficit hyperactivity disorder, congenital heart defects, structural kidney defects, genitourinary problems, immunodeficiency, and a bleeding disorder due to impaired platelet production and function. Previous studies combining both human and animal systems have implicated several disease-causing genes in distal 11q that contribute to the Jacobsen syndrome phenotype. One gene,ETS1, has been implicated in causing congenital heart defects, structural kidney defects, and immunodeficiency. We performed a comprehensive phenotypic analysis on a patient with congenital heart disease previously found to have a de novo frameshift mutation inETS1, resulting in the loss of the DNA-binding domain of the protein. Our results suggest that loss ofEts1causes a “partial Jacobsen syndrome phenotype” including congenital heart disease, facial dysmorphism, intellectual disability, and attention deficit hyperactivity disorder.