PDF(Pubmed)
Abstract：
The term \"autosomal dominant (AD) Alport syndrome\" is often used to describe the condition associated with heterozygous pathogenic COL4A3 or COL4A4 variants and has largely replaced \"thin basement membrane nephropathy (TBMN).\" AD Alport syndrome implies that affected individuals develop end-stage kidney failure (ESKF) as well as the typical Alport hearing loss and ocular abnormalities, but these features have been considered rare with TBMN. Recent studies suggest that ESKF occurs in 14% to 30% of those with heterozygous pathogenic COL4A3 or COL4A4 variants but confirm that the hearing loss and ocular defects occur uncommonly if at all. Uncertainty over the risk of ESKF has persisted. However all the cited studies of heterozygous pathogenic COL4A3 or COL4A4 variants and kidney failure are from hospital-based patients and thus biased toward more severe disease. Multiple unselected cohorts with ESKF have found heterozygous pathogenic variants in COL4A3 and COL4A4 occur about as often as COL4A5 variants, which suggests that AD Alport syndrome causes ESKF as often as X-linked (XL) disease. In the normal population, heterozygous pathogenic COL4A3 and COL4A4 variants are present 20 times more often than COL4A5 variants. Therefore, AD Alport syndrome is complicated by ESKF 20 times less often than XL disease and occurs in fewer than 3% of those with pathogenic COL4A3 or COL4A4 variants by the age of 60. Nevertheless, individuals with heterozygous pathogenic COL4A3 or COL4A4 variants referred to a hospital are still more likely to develop impaired kidney function than those who remain at home undiagnosed.
摘要：
术语“常染色体显性遗传（AD）Alport综合征”通常用于描述与杂合致病性COL4A3或COL4A4变异相关的病症，并已在很大程度上取代了薄基底膜肾病（TBMN）。“ADAlport综合征意味着受影响的个体发展为终末期肾衰竭（ESKF）以及典型的Alport听力损失和眼部异常，但是这些特征在TBMN中被认为是罕见的。最近的研究表明，ESKF发生在14％至30％的具有杂合致病性COL4A3或COL4A4变体的人中，但证实听力损失和眼部缺陷很少发生。ESKF风险的不确定性仍然存在。然而，所有引用的杂合致病性COL4A3或COL4A4变体和肾衰竭的研究都来自医院患者，因此偏向于更严重的疾病。多个未选择的ESKF队列发现COL4A3和COL4A4中的杂合致病变体与COL4A5变体的发生频率相同。这表明ADAlport综合征与X连锁（XL）疾病一样经常引起ESKF。在正常人群中,杂合致病性COL4A3和COL4A4变体的存在频率是COL4A5变体的20倍。因此,ADAlport综合征并发ESKF的频率比XL疾病低20倍，并且在60岁时具有致病性COL4A3或COL4A4变异的患者中发生的比例不到3％。然而，转诊至医院的具有致病性杂合COL4A3或COL4A4变异体的个体仍比那些留在家中未确诊的个体更有可能出现肾功能受损.
