Mutations in the COL4A4 and COL4A3 genes cause familial benign hematuria
Mutations in the COL4A4 and COL4A3 genes cause familial benign hematuria
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DOI：
10.1681/asn.v1351248
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发表时间：
2002-05-01
影响因子：
13.6
通讯作者：
Torra, R
中科院分区：
文献类型：
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作者：
Badenas, C;Praga, M;Torra, R
家族性良性血尿（FBH）是一种常见的常染色体显性遗传病，其特征是存在持续性或复发性血尿。该综合征的临床和病理特征与早期Alport综合征（AS）相似，因此提出了一种共同的分子缺陷。COL4A3/4基因似乎与常染色体AS和FBH有关。这项研究包括对COL4A3/4基因座的连锁分析，并在11个活检证实的FBH家族中寻找这些基因的突变。单倍型分析显示，9个家族中有8个家族与COL4A3/4位点存在连锁。有一个家庭与这个基因位点没有关联：然而，它包括三名可能是x连锁AS携带者的受影响妇女。两个家族太小，无法进行连锁分析，COL4A3和COL4A4突变筛查发现6个新的致病突变，2个在COL4A3基因（G985V和G1015E）， 4个在COL4A4基因（3222insA、IVS23-1G>C、31del11和G960R）。这是首次在FBH家族中发现COL4A3基因突变。本研究明确了COL4A4和COL4A3基因在FBH发病中的主要作用。
Familial benign hematuria (FBH) is a common autosomal dominant disorder characterized by the presence of persistent or recurrent hematuria. The clinical and pathologic features of this syndrome resemble those of early Alport syndrome (AS), and for this reason a common molecular defect has been proposed. The COL4A3/4 genes seem to be involved in both autosomal AS and FBH. This study involves a linkage analysis for the COL4A3/4 loci and a search for mutations within these genes in 11 biopsy-proven FBH families. Haplotype analysis showed that linkage to the COL4A3/4 locus could not be excluded in eight of nine families. One family was not linked to this locus: however, it included three affected women who could be X-linked AS carriers. Two families were too small to perform linkage analysis, COL4A3 and COL4A4 mutation screening disclosed six new pathogenic mutations, two in the COL4A3 gene (G985V and G1015E) and four in the COL4A4 gene (3222insA, IVS23-1G>C, 31del11, and G960R). It is the first time that mutations within the COL4A3 gene are described in families with FBH. This study clearly demonstrates the main role of the COL4A4 and COL4A3 genes in the pathogenesis of FBH.