X-linked Alport syndrome:: Natural history and genotype-phenotype correlations in girls and women belonging to 195 families:: A "European community Alport syndrome concerted action" study
X-linked Alport syndrome:: Natural history and genotype-phenotype correlations in girls and women belonging to 195 families:: A "European community Alport syndrome concerted action" study
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DOI：
10.1097/01.asn.0000090034.71205.74
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发表时间：
2003-10-01
影响因子：
13.6
通讯作者：
Gubler, MC
中科院分区：
文献类型：
--
作者：
Jais, JP;Knebelmann, B;Gubler, MC
Alport综合征（AS）是一种IV型胶原遗传性疾病，其特征在于进行性血尿肾炎、听力丧失和眼部改变。COL 4A 5胶原基因的突变导致了更常见的X连锁显性形式的疾病，其特征是女孩和妇女的疾病严重程度要低得多。一个“欧洲共同体Alport综合征协调行动”（ECASCA）小组成立，以描绘Alport综合征表型在每个性别和确定基因型-表型的相关性，在大量的家庭。收集了有关329个家庭的数据，其中250个家庭存在X连锁传播。属于195个家庭的杂合子女孩和妇女的特征与证明COL 4A 5突变的半合子男孩和男人进行了比较。95%的携带者出现血尿，而其他人则始终没有血尿。蛋白尿、听力丧失和眼部缺陷的发生率分别为75%、28%和15%。在40岁之前，女孩和妇女患终末期肾病或耳聋的概率分别为12%和10%，而男孩和男子分别为90%和80%。女性在60岁以后进展为终末期肾病的风险似乎增加。由于缺乏基因型-表型相关性和大的家族内表型异质性，X连锁Alport综合征携带者疾病的早期预后仍无实际意义。肾功能衰竭的危险因素已经确定：蛋白尿的发生和进行性增加，以及听力缺陷的发展。
Alport syndrome (AS) is a type IV collagen hereditary disease characterized by progressive hematuric nephritis, hearing loss, and ocular changes. Mutations in the COL4A5 collagen gene are responsible for the more common X-linked dominant form of the disease characterized by much less severe disease in girls and women. A "European Community Alport Syndrome Concerted Action" (ECASCA) group was established to delineate the Alport syndrome phenotype in each gender and to determine genotype-phenotype correlations in a large number of families. Data concerning 329 families, 250 of them with an X-linked transmission, were collected. Characteristics of heterozygous girls and women belonging to the 195 families with proven COL4A5 mutation are compared with those of hemizygous boys and men. Hematuria was observed in 95% of carriers and consistently absent in the others. Proteinuria, hearing loss, and ocular defects developed in 75%, 28%, and 15%, respectively. The probability of developing end-stage renal disease or deafness before the age of 40 yr was 12% and 10%, respectively, in girls and women versus 90 and 80%, respectively, in boys and men. The risk of progression to end-stage renal disease appears to increase after the age of 60 yr in women. Because of the absence of genotype-phenotype correlation and the large intrafamilial phenotypic heterogeneity, early prognosis of the disease in X-linked Alport syndrome carriers remains moot. Risk factors for developing renal failure have been identified: the occurrence and progressive increase in proteinuria, and the development of a hearing defect.