A novel germline GATA2 frameshift mutation with a premature stop codon in a family with congenital sensory hearing loss and myelodysplastic syndrome
A novel germline GATA2 frameshift mutation with a premature stop codon in a family with congenital sensory hearing loss and myelodysplastic syndrome
复制标题
先天性感觉性听力损失和骨髓增生异常综合征家族中一种新型种系 GATA2 移码突变，具有提前终止密码子
DOI：
10.1007/s12185-021-03130-w
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发表时间：
2021
影响因子：
2.1
通讯作者：
Ishida Fumihiro
中科院分区：
文献类型：
--
作者：
Nakazawa Hideyuki;Yamaguchi Tomomi;Sakai Hitoshi;Maruyama Masae;Kawakami Toru;Kawakami Fumihiro;Nishina Sayaka;Ishikawa Masumi;Kosho Tomoki;Ishida Fumihiro
GATA2是一种调节早期造血和发育过程的锌指转录因子。 GATA2 杂合种系突变是多效性常染色体显性遗传疾病（GATA2 缺乏综合征）的基础。其广泛的临床特征涉及骨髓增生异常综合征（MDS）/急性髓系白血病（AML）的家族易感性和多器官功能障碍，包括先天性感音神经性听力损失（CSHL）。我们在此报告了一个具有新种系移码突变的谱系，表现为 CSHL 和家族性 MDS。先证者是一名 46 岁男性，他的女儿也出现了一组相同的临床综合征。目标 DNA 测序在 GATA2 基因的外显子 5 (NM_032638.4:c.1126_1133dup:p.Lys378Asnfs*12) 处发现了一个新的八核苷酸重复插入。 RT-PCR和亚克隆分析表明，移码可能导致带有早期终止密码子的截短突变，而不干扰预测的剪接位点。预测的突变蛋白有 388 个氨基酸，计算机分析显示该变体被认为是有害的。在未受影响的家庭成员中未检测到这种突变。它的有害影响很可能预示着该谱系中的家族性 MDS 和 CSHL。可能需要对可疑个体进行基因检测以进行适当的管理，包括及时移植。
GATA2is a zinc-finger transcription factor regulating early hematopoiesis and developmental processes. Heterozygous germline mutations inGATA2underlie a pleiotropic autosomal dominant disorder, GATA2 deficiency syndrome. The wide spectrum of its clinical features involves familial predisposition to myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML) and multiorgan dysfunction, including congenital sensorineural hearing loss (CSHL). We herein report a pedigree with a novel germline frameshift mutation presenting as CSHL and familial MDS. The proband was a 46-year-old man, and his daughter also presented with an identical set of clinical syndromes. Target DNA sequencing identified a novel eight-nucleotide duplicative insertion at exon 5 (NM_032638.4:c.1126_1133dup:p.Lys378Asnfs*12) of theGATA2gene. RT-PCR and subcloning analysis showed that the frameshift might result in a truncated mutation with an early stop codon without interfering with the predicted splice site. The predicted mutant protein had 388 amino acids and in silico analysis showed the variant was considered deleterious. This mutation was not detected in unaffected family members. Its deleterious effect is highly likely to have portended the familial MDS and CSHL in this pedigree. Genetic testing among suspected individuals may be warranted for adequate management, including timely transplantation.
影响因子：
20.3
作者：
Spinner, Michael A.;Sanchez, Lauren A.;Holland, Steven M.
通讯作者：
Holland, Steven M.
影响因子：
20.3
作者：
Hsu, Amy P.;Sampaio, Elizabeth P.;Holland, Steven M.
通讯作者：
Holland, Steven M.