DELETIONS IN THE COL4A5 COLLAGEN GENE IN X-LINKED ALPORT SYNDROME - CHARACTERIZATION OF THE PATHOLOGICAL TRANSCRIPTS IN NONRENAL CELLS AND CORRELATION WITH DISEASE EXPRESSION
DELETIONS IN THE COL4A5 COLLAGEN GENE IN X-LINKED ALPORT SYNDROME - CHARACTERIZATION OF THE PATHOLOGICAL TRANSCRIPTS IN NONRENAL CELLS AND CORRELATION WITH DISEASE EXPRESSION
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DOI：
10.1172/jci117073
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发表时间：
1994-03-01
影响因子：
15.9
通讯作者：
GUBLER, MC
中科院分区：
文献类型：
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作者：
ANTIGNAC, C;KNEBELMANN, B;GUBLER, MC
应用COL4A5 cDNA探针，通过Southern印迹分析，检测了88例X连锁Alport综合征无亲缘关系的男性患者的IV型胶原α 5链（COL4A5）基因的主要基因重排。检测到14种不同的缺失，在患者群体中提供了16%的COL4A5基因缺失率。缺失以不同的大小分散在整个基因上，范围从1 kb到一个患者中完全缺失基因（> 250 kb）。在4例基因内缺失的患者中，免疫组化研究证明肾小球基底膜中没有α 3（IV）链。这一发现支持了α 5（IV）链异常可能阻止α 3（IV）链正常掺入肾小球基底膜的假设。直接测序的cDNA扩增的淋巴母细胞mRNA的4例患者的内部基因缺失，使用适当的组合引物扩增跨越预测的边界的缺失，使我们能够确定的效果的基因组重排的成绩单，并推断，在α 5（IV）链。无论缺失的程度和推定的蛋白质产物如何，14个缺失发生在青少年型Alport综合征患者中。
The type IV collagen alpha 5 chain (COL4A5) gene of 88 unrelated male patients with X-linked Alport syndrome was tested for major gene rearrangements by Southern blot analysis, using COL4A5 cDNA probes. 14 different deletions were detected, providing a 16% deletion rate in the COL4A5 gene in the patient population. The deletions are dispersed all over the gene with different sizes, ranging from 1 kb to the complete absence of the gene (> 250 kb) in one patient. In four patients with intragenic deletions, absence of the alpha 3(IV) chain in the glomerular basement membrane was demonstrated by immunohistochemical studies. This finding supports the hypothesis that abnormalities in the alpha 5(TV) chain may prevent normal incorporation of the alpha 3(IV) chain into the glomerular basement membrane. Direct sequencing of cDNA amplified from lymphoblast mRNA of four patients with internal gene deletions, using appropriate combinations of primers amplifying across the predicted boundaries of the deletions, allowed us to determine the effect of the genomic rearrangements on the transcripts and, by inference, on the alpha 5(IV) chain. Regardless of the extent of deletion and of the putative protein product, the 14 deletions occur in patients with juvenile-type Alport syndrome.