DGGE screening of PKD1 gene reveals novel mutations in a large cohort of 146 unrelated patients
DGGE screening of PKD1 gene reveals novel mutations in a large cohort of 146 unrelated patients
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DOI：
10.1007/s004390051094
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发表时间：
1999-09-01
期刊：
影响因子：
5.3
通讯作者：
Ferec, C
中科院分区：
文献类型：
--
作者：
Perrichot, RA;Mercier, B;Ferec, C
常染色体显性遗传性多囊肾病（ADPKD）是最常见的遗传性肾脏疾病之一。ADPKD是一种遗传异质性疾病，涉及至少三种不同的基因。PKD 1是定位于染色体16p13.3的主要基因座，约占ADPKD病例的85%。寻找突变是理解ADPKD潜在分子机制的重要一步。尽管许多研究小组进行了密集的筛选，但到目前为止只有少数突变被描述。我们进行了第一项研究，使用变性梯度凝胶电泳（DGGE）扫描PKD 1基因的非重复区域的突变在一个大队列的146名法国无关ADPKD患者。我们成功地鉴定了新的突变：3个是移码突变，2个无义突变，2个错义突变，1个是9个核苷酸的框架内插入，3个内含子变异和几个多态性。其中一个突变是该基因中描述的第四个从头突变。我们还描述了一个家庭可能的临床预期。DGGE是检测PKD 1基因核苷酸变化的有效方法。
Autosomal dominant polycystic kidney disease (ADPKD) is one of the most commonly inherited renal diseases. ADPKD is a genetically heterogeneous disorder involving at least three different genes. PKD1, the major locus mapped to chromosome 16p13.3 accounts for approximately 85% of ADPKD cases. The search for mutations is a very important step in understanding the molecular mechanisms underlying ADPKD. Despite intense screening by many groups, only a small number of mutations have been described so far. We undertook the first study using denaturing gradient gel electrophoresis (DGGE) to scan for mutations in the non-duplicated region of the PKD1 gene in a large cohort of 146 French unrelated ADPKD patients. We successfully identified novel mutations: 3 are frameshift mutations, 2 nonsense: mutations, 2 missense mutations, 1 is an insertion in the frame of 9 nucleotides, 3 intronic variations and several polymorphisms. One of these mutations is the fourth de novo mutation described in this gene. We also describe a family with possible clinical anticipation. DGGE is an effective method for detecting nucleotide changes in the PKD1 gene.