UBA2 variants underlie a recognizable syndrome with variable aplasia cutis congenita and ectrodactyly.
UBA2 variants underlie a recognizable syndrome with variable aplasia cutis congenita and ectrodactyly.
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UBA 2变异是一种可识别的先天性皮肤发育不全和缺指综合征的基础。
DOI：
10.1038/s41436-021-01182-1
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发表时间：
2021-09
期刊：
影响因子：
--
通讯作者：
Hufnagel RB
中科院分区：
文献类型：
--
作者：
Schnur RE;Yousaf S;Liu J;Chung WK;Rhodes L;Marble M;Zambrano RM;Sobreira N;Jayakar P;Pierpont ME;Schultz MJ;Pichurin PN;Olson RJ;Graham GE;Osmond M;Contreras-García GA;Campo-Neira KA;Peñaloza-Mantilla CA;Flage M;Kuppa S;Navarro K;Sacoto MJG;Wentzensen IM;Scarano MI;Juusola J;Prada CE;Hufnagel RB
人类染色体19q13.11缺失综合征与包括先天性皮肤发育不全（ACC）和缺指（趾）作为特异性特征的可变表型相关。UBA 2（泛素样修饰激活酶2）位于最小缺失重叠区附近。我们的目标是确定UBA 2相关的表型谱在人类和斑马鱼由于序列变异，并建立疾病的机制。应用外显子组测序技术检测7个家系16名受试者的UBA 2基因序列变异。uba 2功能丧失在斑马鱼中进行了建模。在斑马鱼拯救实验中评估了人类错义变体的影响。检测到7个人UBA 2功能丧失和错义序列变体。UBA 2-表型包括ACC、缺指、神经发育异常、外胚层、骨骼、颅面、心脏、肾脏和生殖器异常。UBA 2在斑马鱼的眼、脑和胸鳍中表达; UBA 2缺失的鱼表现出生长不足、小头畸形、小眼畸形、下颌发育不全和鳍异常。uba 2-mRNAs与人类错义变异体未能挽救失合子斑马鱼表型。UBA 2变异体引起具有广泛表型谱的可识别综合征。我们的数据表明，UBA 2功能的丧失是人类UBA 2单基因疾病的基础，并强调了SUMO化在受影响组织发育中的重要性。
The human chromosome 19q13.11 deletion syndrome is associated with a variable phenotype that includes aplasia cutis congenita (ACC) and ectrodactyly as specific features. UBA2 (ubiquitin-like modifier-activating enzyme 2) lies adjacent to the minimal deletion overlap region. We aim to define the UBA2-related phenotypic spectrum in humans and zebrafish due to sequence variants and to establish the mechanism of disease. Exome Sequencing was used to detect UBA2 sequence variants in 16 subjects in 7 unrelated families. uba2 loss-of-function was modeled in zebrafish. Effects of human missense variants were assessed in zebrafish rescue experiments. 7 human UBA2 loss-of-function and missense sequence variants were detected. UBA2-phenotypes included ACC, ectrodactyly, neurodevelopmental abnormalities, ectodermal, skeletal, craniofacial, cardiac, renal, and genital anomalies. uba2 was expressed in zebrafish eye, brain, and pectoral fins; uba2-null fish showed deficient growth, microcephaly, microphthalmia, mandibular hypoplasia, and abnormal fins. uba2-mRNAs with human missense variants failed to rescue nullizygous zebrafish phenotypes. UBA2 variants cause a recognizable syndrome with a wide phenotypic spectrum. Our data suggest that loss of UBA2 function underlies the human UBA2 monogenic disorder and highlights the importance of SUMOylation in the development of affected tissues.
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影响因子：
0.7
作者：
Abe KT;Rizzo IMPO;Coelho ALV;Sakai N Jr;Carvalho DR;Speck-Martins CE
通讯作者：
Speck-Martins CE
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1.3
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Carreira IM
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Meng XW
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4.6
作者：
Liedtke, Daniel;Orth, Melanie;Klopocki, Eva
通讯作者：
Klopocki, Eva
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1.9
作者：
Aerden, Mio;Bauters, Marijke;Devriendt, Koenraad
通讯作者：
Devriendt, Koenraad