Missense mutation and hexanucleotide duplication in the PAX2 gene in two unrelated families with renal-coloboma syndrome (MIM 120330)
Missense mutation and hexanucleotide duplication in the PAX2 gene in two unrelated families with renal-coloboma syndrome (MIM 120330)
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DOI：
10.1007/s004390050798
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发表时间：
1998-08-01
期刊：
影响因子：
5.3
通讯作者：
Leys, A
中科院分区：
文献类型：
--
作者：
Devriendt, K;Matthijs, G;Leys, A
我们报告一个常染色体显性遗传性肾功能不全家系，由肾发育不良引起，共6例。在所有受影响的个体中，都检测到视盘发育不良的迹象，但大多数患者没有症状。PAX2基因的杂合错义突变导致Gly75到Ser的替换在所有受影响的个体中都存在。第二个无关患者的眼部症状与视盘发育不良有关，并有膀胱输尿管返流的病史。在PAX2基因中检测到杂合性六核苷酸重复，导致GluThr在第74和75位重复。这两个家族中的突变是PAX2基因中第一个不会导致蛋白质截断的突变。从机制上讲，这些突变预计会导致PAX2蛋白的异常折叠。这些观察进一步扩大了与PAX2突变相关的临床特征的频谱，并表明通过仔细的眼睛检查，可以在肾发育不良患者中发现一种独特的遗传疾病。由于此综合征的眼部表现为视网膜和视盘发育不良的各种异常，我们倾向于使用“乳头肾综合征”这个术语。
We present a family with autosomal-dominant inheritance of renal insufficiency caused by renal hypoplasia in six individuals. In all affected individuals, signs of optic disk dysplasia were detected, but most patients were asymptomatic. A heterozygous missense mutation in the PAX2 gene causing a Gly75 to Ser substitution was present in all affected individuals. A second, unrelated patient presented with ocular complaints related to optic disk dysplasia, and had a history of vesico-ureteral reflux. A heterozygous hexanucleotide duplication in the PAX2 gene was detected leading to the duplication of GluThr at positions 74 and 75. The mutations in these two families are the first mutations in the PAX2 gene that do not lead to a truncated protein. Mechanistically, these mutations are expected to result in abnormal folding of the PAX2 protein. These observations further expand the spectrum of clinical features associated with PAX2 mutations, and suggest that a distinct genetic disorder can be identified in patients with renal dysplasia through a careful eye examination. As the ocular manifestations in this syndrome are variable anomalies of retinal and optic disk dysplasia, we prefer the term "papillorenal syndrome".