Identification of a gene disrupted by inv(11)(q13.5;q25) in a patient with left-right axis malformation
Identification of a gene disrupted by inv(11)(q13.5;q25) in a patient with left-right axis malformation
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DOI：
10.1007/s004390051038
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发表时间：
2000-03-01
期刊：
影响因子：
5.3
通讯作者：
Nakamura, Y
中科院分区：
文献类型：
--
作者：
Iida, A;Emi, M;Nakamura, Y
在一名9个月大的男性患者中发现了inv（11）（q13.5;q25）倒置，该患者患有复杂的紫绀型心脏缺陷、改变的肺分叶、对称的肝脏和异常分叶的脾脏（多脾）。这种染色体重排遗传自表型正常的父亲。我们将这些区域称为DHTX-A（在异位中被破坏）- A（11q13.5）和DHTX-B（11 q25）。在这里，我们报告的分离和表征的倒位断裂点和被破坏的DHTX-A断裂点的基因。推定的DHTX与UVRAG基因相同，UVRAG基因最初被鉴定为补充着色性干皮病互补组C的UV敏感性的基因。发现4-kb的mRNA由一个大基因编码，至少300 kb长，由15个外显子组成。基因产物的功能在很大程度上仍然未知。然而，UVRAG蛋白的近中心部分被预测含有卷曲螺旋结构域，其已经涉及介导蛋白质-蛋白质相互作用。Southern分析和荧光原位杂交（FISH）显示，DHTX-A断裂点在病人和他的父亲位于内含子之间的UVRAG外显子6和7。北方印迹分析表明，在人胎儿和成人组织和小鼠胚胎第7天和成人组织中，分别强表达。全胚原位杂交结果也表明，Uvrag基因在胚前体阶段表达。几个假说进行了讨论，以解释染色体倒位和伴随的表型之间的关系。
An inv(11)(q13.5;q25) inversion was previously identified in a 9-month-old male patient with complex cyanotic heart defects, altered lung lobation, sym metric liver, and abnormally lobulated spleen (polysplenia). This chromosomal rearrangement was inherited from the phenotypically normal father. We termed these regions DHTX-A (disrupted in heterotaxy)- A at 11q13.5 and DHTX-B at 11q25. Here, we report the isolation and characterization of the inversion breakpoints and the gene that is disrupted by the DHTX-A breakpoint. The putative DHTX is identical to the UVRAG gene, which was originally identified as a gene that complements the UV sensitivity of xeroderma pigmentosum complementation group C. The 4-kb mRNA was found to be encoded by a large gene, at least 300 kb long, composed of 15 exons. The function of the gene product remains largely unknown. However, the near central portion of the UVRAG protein is predicted to contain a coiled-coil domain, which has been implicated in mediating protein-protein interactions. Southern analyses and fluorescence in situ hybridization (FISH) revealed that the DHTX-A breakpoint in the patient and his father lies within the intron between exons 6 and 7 of UVRAG. Northern blot analysis indicated strong expression in human fetal and adult tissues and in mouse embryonic day-7 and adult tissues, respectively. Whole mount in situ hybridization also showed that the Uvrag gene is expressed in the presomite-stage embryo. Several hypotheses are discussed to explain the relationship between the chromosomal inversion and the accompanying phenotypes.