Mutation Analysis of Autosomal-Dominant Polycystic Kidney Disease Patients.
Mutation Analysis of Autosomal-Dominant Polycystic Kidney Disease Patients.
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常染色体显性多囊肾病（ADPKD）的特征是双侧肾囊肿，最终导致终末期肾病。虽然ADPKD的主要致病基因是PKD 1和PKD 2，但其他基因也被认为参与其中。50例ADPKD患者通过外显子组测序或多重连接依赖性探针扩增（MLPA），然后通过长聚合酶链反应和桑格测序进行分析。在35例患者（70%）中检测到PKD1或PKD2或GANAB的变异体。外显子组测序在30例患者中分别鉴定了PKD1、PKD2和GANAB的24、7和1个变体。MLPA分析确定了三名患者PKD1和两名患者PKD2的大缺失。我们在15例外显子组测序和MLPA分析阴性的患者中搜索了90个囊肿相关基因，并确定了17个罕见变异。根据美国医学遗传学和基因组学学会的指导方针，其中四种被认为是“可能致病的”或“致病的”变异。在11名无家族史的患者中，分别在PKD 1、PKD 2和其他基因中发现了4个、2个和4个变异，而在1名患者中未发现致病基因。虽然应该仔细评估这些基因中每个变体的致病性，但在非典型ADPKD病例中，全面的遗传分析可能是有用的。
Autosomal-dominant polycystic kidney disease (ADPKD) is characterized by bilateral kidney cysts that ultimately lead to end-stage kidney disease. While the major causative genes of ADPKD are PKD1 and PKD2, other genes are also thought to be involved. Fifty ADPKD patients were analyzed by exome sequencing or multiplex ligation-dependent probe amplification (MLPA), followed by long polymerase chain reaction and Sanger sequencing. Variants in PKD1 or PKD2 or GANAB were detected in 35 patients (70%). Exome sequencing identified 24, 7, and 1 variants in PKD1, PKD2, and GANAB, respectively, in 30 patients. MLPA analyses identified large deletions in PKD1 in three patients and PKD2 in two patients. We searched 90 cyst-associated genes in 15 patients who were negative by exome sequencing and MLPA analyses, and identified 17 rare variants. Four of them were considered “likely pathogenic” or “pathogenic” variants according to the American College of Medical Genetics and Genomics guidelines. Of the 11 patients without a family history, four, two, and four variants were found in PKD1, PKD2, and other genes, respectively, while no causative gene was identified in one patient. While the pathogenicity of each variant in these genes should be carefully assessed, a comprehensive genetic analysis may be useful in cases of atypical ADPKD.
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影响因子：
16.6
作者：
Bizet AA;Becker-Heck A;Ryan R;Weber K;Filhol E;Krug P;Halbritter J;Delous M;Lasbennes MC;Linghu B;Oakeley EJ;Zarhrate M;Nitschké P;Garfa-Traore M;Serluca F;Yang F;Bouwmeester T;Pinson L;Cassuto E;Dubot P;Elshakhs NAS;Sahel JA;Salomon R;Drummond IA;Gubler MC;Antignac C;Chibout S;Szustakowski JD;Hildebrandt F;Lorentzen E;Sailer AW;Benmerah A;Saint-Mezard P;Saunier S
通讯作者：
Saunier S
影响因子：
2.3
作者：
Mochizuki, Toshio;Teraoka, Atsuko;Nitta, Kosaku
通讯作者：
Nitta, Kosaku
影响因子：
9.8
作者：
Sampson, JR;Maheshwar, MM;Harris, PC
通讯作者：
Harris, PC
影响因子：
4.4
作者：
Kozlowski, Piotr;Bissler, John;Kwiatkowski, David J.
通讯作者：
Kwiatkowski, David J.
影响因子：
9.8
作者：
Macia, Maxence S.;Halbritter, Jan;Benmerah, Alexandre
通讯作者：
Benmerah, Alexandre