Different mutations in the COL4A5 collagen gene in two patients with different features of Alport syndrome.
Different mutations in the COL4A5 collagen gene in two patients with different features of Alport syndrome.
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DOI：
10.1038/ki.1992.264
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发表时间：
1992-07
影响因子：
19.6
通讯作者：
H. Smeets;J. Melenhorst;H. Lemmink;C. Schröder;M. Nelen;J. Zhou;S. L. Hostikka;K. Tryggvason;H. Ropers;M. Jansweijer
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文献类型：
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作者：
H. Smeets;J. Melenhorst;H. Lemmink;C. Schröder;M. Nelen;J. Zhou;S. L. Hostikka;K. Tryggvason;H. Ropers;M. Jansweijer
两名具有不同Alport综合征特征的患者中COL 4A 5胶原基因的不同突变Alport综合征是一种遗传性肾脏疾病，其中进行性肾功能衰竭常伴有感音神经性耳聋和眼部异常。最近，在Alport综合征患者中检测到IV型胶原α5链基因突变。我们在18名无关患者中寻找该基因的突变，并在两名患者中检测到异常。在患者BB的基因中，我们确定了一个复杂的缺失，其中包括编码非胶原结构域和部分胶原区域的外显子。该患者表现为早发性肾炎（17岁时的终末期肾病）伴耳聋。在接受了一个无关捐赠者的肾脏后一年内，他患上了抗肾小球基底膜肾炎。在患者WJ中检测到点突变，将非胶原结构域中的丝氨酸改变为丝氨酸。他的临床特征较轻（33岁时肾衰竭，无听力损失），近期肾移植未引起抗肾小球基底膜疾病。这些初步数据表明，非胶原结构域破坏程度的差异可能与Alport综合征的严重程度和/或异质性以及肾移植物中肾炎的发生相关。
Different mutations in the COL4A5 collagen gene in two patients with different features of Alport syndrome. Alport syndrome is a hereditary renal disease in which progressive renal failure is often accompanied by sensorineural deafness and ocular abnormalities. Recently, mutations were detected in the type IV collagen α5 chain gene in Alport syndrome patients. We searched for mutations in this gene in 18 unrelated patients, and in two patients abnormalities were detected. In the gene of patient BB we identified a complex deletion, which included the exons encoding the non-collagenous domain and part of the collagenous region. This patient showed early onset nephritis (end-stage renal disease at 17 years) with deafness. Within a year after receiving a kidney from an unrelated donor, he developed an antiglomerular basement membrane nephritis. In patient WJ a point-mutation was detected, changing a tryptophane into a serine in the non-collagenous domain. His clinical features are milder (renal failure at 33 years, no hearing loss), and a recent renal allograft did not provoke antiglomerular basement membrane disease. These initial data suggest that differences in the extent of disruption of the non-collagenous domain may correlate with the severity and/or heterogeneity of Alport syndrome and with the development of nephritis in renal allografts.