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BMC Medical Genetics

, 12:164

Clinical-Molecular Genetics and Cytogenetics


BackgroundAutosomal dominant polycystic kidney disease ADPKD is the most common inherited renal disease with an incidence of 1 in 400 to 1000. The disease is genetically heterogeneous, with two genes identified: PKD1 16p13.3 and PKD2 4q21. Molecular diagnosis of the disease in at-risk individuals is complicated due to the structural complexity of PKD1 gene and the high diversity of the mutations. This study is the first systematic ADPKD mutation analysis of both PKD1 and PKD2 genes in Chinese patients using denaturing high-performance liquid chromatography DHPLC.

MethodsBoth PKD1 and PKD2 genes were mutation screened in each proband from 65 families using DHPLC followed by DNA sequencing. Novel variations found in the probands were checked in their family members available and 100 unrelated normal controls. Then the pathogenic potential of the variations of unknown significance was examined by evolutionary comparison, effects of amino acid substitutions on protein structure, and effects of splice site alterations using online mutation prediction resources.

ResultsA total of 92 variations were identified, including 27 reported previously. Definitely pathogenic mutations ten frameshift, ten nonsense, two splicing defects and one duplication were identified in 28 families, and probably pathogenic mutations were found in an additional six families, giving a total detection level of 52.3% 34-65. About 69% 20-29 of the mutations are first reported with a recurrent mutation rate of 31%.

ConclusionsMutation study of PKD1 and PKD2 genes in Chinese Hans with ADPKD may contribute to a better understanding of the genetic diversity between different ethnic groups and enrich the mutation database. Besides, evaluating the pathogenic potential of novel variations should also facilitate the clinical diagnosis and genetic counseling of the disease.

Electronic supplementary materialThe online version of this article doi:10.1186-1471-2350-12-164 contains supplementary material, which is available to authorized users.

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Autor: Chaowen Yu - Yuan Yang - Lin Zou - Zhangxue Hu - Jing Li - Yunqiang Liu - Yongxin Ma - Mingyi Ma - Dan Su - Sizhong Zhan


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