Background

Mutation screening of autosomal dominant polycystic kidney disease (ADPKD) cases imply the major involvement of PKD1 mutations in 85% of patients while rest of the cases harbor mutation in PKD2, DNAJB11 and GANAB. This essentially indicates that individual’s genotype holds the key for disease susceptibility and its severity.

Methods

For finding genetic variability underlying the disease pathophysiology, 84 Indian ADPKD cases, 31 family members (12 susceptible) and 122 age matched control were screened for PKD1 and PKD2 using Sanger sequencing, PCR-RFLP and ARMS-PCR.

Results

Genetic screening of Indian ADPKD cases revealed total 67 variants in PKD1 and 28 variants in PKD2. Among the identified variants in PKD1 and PKD2 genes, 35.79% were novel variants and 64.2% recurrent. Further, subcategorization of PKD1 variants showed 14 truncation/frameshift, 21 nonsynonymous, 25 synonymous and 7 intronic variants. Moreover, we observed 40 families with PKD1 pathogenic variants, 7 families with PKD2 pathogenic variants, 9 families with PKD1 & PKD2 pathogenic variants, and 26 families with PKD1/PKD2/PKD1-PKD2 non-pathogenic genetic variants.

Conclusion

Present study represented genetic background of Indian ADPKD cases which will be helpful in disease management as well as finding the genetically matched donor for kidney transplant.

中文翻译：

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在印度ADPKD患者中对PKD1和PKD2进行突变筛选，鉴定出95种遗传变异。

背景

常染色体显性遗传性多囊肾病（ADPKD）病例的突变筛查表明85％的患者主要参与PKD1突变，而其余病例的PKD2，DNAJB11和GANAB则具有突变。这实质上表明，个体的基因型是疾病易感性及其严重性的关键。

方法

为了发现疾病病理生理学的遗传变异性，使用Sanger测序，PCR-RFLP和ARMS-PCR对84例印度ADPKD病例，31个家庭成员（12个易感人群）和122个年龄匹配的对照进行了PKD1和PKD2筛选。

结果

印度ADPKD病例的遗传筛查显示PKD1共67个变异，PKD2共28个变异。在PKD1和PKD2基因的已鉴定变体中，新变体占35.79％，复发性占64.2％。此外，PKD1变体的亚分​​类显示14个截断/移码，21个非同义词，25个同义词和7个内含子变体。此外，我们观察到40个具有PKD1致病性变体的家庭，7个具有PKD2致病性变体的家庭，9个具有PKD1和PKD2致病性变体的家庭和26个具有PKD1 / PKD2 / PKD1-PKD2非致病性遗传变体的家庭。

结论

本研究代表了印度ADPKD病例的遗传背景，这将有助于疾病管理以及寻找基因匹配的肾脏移植供体。