A new atypical splice mutation in PKD2 leading to autosomal dominant polycystic kidney disease in a Chinese family
Introduction: Autosomal dominant polycystic kidney disease (ADPKD) is a very common hereditary renal disorder. Mutations in PKD1 and PKD2, identified as disease-causing genes, account for 85% and 15% of the ADPKD cases, respectively. Methods: In this study, the mutation analysis of polycystic kidney...
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| Format: | Article |
| Language: | English |
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Wolters Kluwer – Medknow Publications
2024-04-01
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| Series: | Singapore Medical Journal |
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| Online Access: | https://journals.lww.com/10.11622/smedj.2021162 |
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| author | Junlin Zhang Yiting Wang Yingwang Zhao Fang Liu |
| author_facet | Junlin Zhang Yiting Wang Yingwang Zhao Fang Liu |
| author_sort | Junlin Zhang |
| collection | DOAJ |
| description | Introduction:
Autosomal dominant polycystic kidney disease (ADPKD) is a very common hereditary renal disorder. Mutations in PKD1 and PKD2, identified as disease-causing genes, account for 85% and 15% of the ADPKD cases, respectively.
Methods:
In this study, the mutation analysis of polycystic kidney disease (PKD) genes was performed in a Chinese family with suspected ADPKD using targeted clinical exome sequencing (CES). The candidate pathogenic variants were further tested by using Sanger sequencing and validated for co-segregation. In addition, reverse transcription-polymerase chain reaction (RT-PCR) was performed to test for abnormal splicing and assess its potential pathogenicity.
Results:
A novel atypical splicing mutation that belongs to unclassified variants (UCVs), IVS6+5G>C, was identified in three family members by CES and was shown to co-segregate only with the affected individuals. The RT-PCR revealed the abnormal splicing of exon 6, which thus caused truncating mutation. These findings suggested that the atypical splice site alteration, IVS6+5G>C, in the PKD2 gene was the potential pathogenic mutation leading to ADPKD in this Chinese family.
Conclusion:
The data available in this study provided strong evidence that IVS6+5G>C is the potential pathogenic mutation for ADPKD. In addition, our findings emphasised the significance of functional analysis of UCVs and genotype–phenotype correlation in ADPKD. |
| format | Article |
| id | doaj-art-686e7b4ce97040f1b5bc908e81288573 |
| institution | Kabale University |
| issn | 0037-5675 2737-5935 |
| language | English |
| publishDate | 2024-04-01 |
| publisher | Wolters Kluwer – Medknow Publications |
| record_format | Article |
| series | Singapore Medical Journal |
| spelling | doaj-art-686e7b4ce97040f1b5bc908e812885732025-02-09T10:21:45ZengWolters Kluwer – Medknow PublicationsSingapore Medical Journal0037-56752737-59352024-04-0165422923410.11622/smedj.2021162A new atypical splice mutation in PKD2 leading to autosomal dominant polycystic kidney disease in a Chinese familyJunlin ZhangYiting WangYingwang ZhaoFang LiuIntroduction: Autosomal dominant polycystic kidney disease (ADPKD) is a very common hereditary renal disorder. Mutations in PKD1 and PKD2, identified as disease-causing genes, account for 85% and 15% of the ADPKD cases, respectively. Methods: In this study, the mutation analysis of polycystic kidney disease (PKD) genes was performed in a Chinese family with suspected ADPKD using targeted clinical exome sequencing (CES). The candidate pathogenic variants were further tested by using Sanger sequencing and validated for co-segregation. In addition, reverse transcription-polymerase chain reaction (RT-PCR) was performed to test for abnormal splicing and assess its potential pathogenicity. Results: A novel atypical splicing mutation that belongs to unclassified variants (UCVs), IVS6+5G>C, was identified in three family members by CES and was shown to co-segregate only with the affected individuals. The RT-PCR revealed the abnormal splicing of exon 6, which thus caused truncating mutation. These findings suggested that the atypical splice site alteration, IVS6+5G>C, in the PKD2 gene was the potential pathogenic mutation leading to ADPKD in this Chinese family. Conclusion: The data available in this study provided strong evidence that IVS6+5G>C is the potential pathogenic mutation for ADPKD. In addition, our findings emphasised the significance of functional analysis of UCVs and genotype–phenotype correlation in ADPKD.https://journals.lww.com/10.11622/smedj.2021162atypical splice mutationautosomal dominant polycystic kidney diseasegenetic testpkd genes |
| spellingShingle | Junlin Zhang Yiting Wang Yingwang Zhao Fang Liu A new atypical splice mutation in PKD2 leading to autosomal dominant polycystic kidney disease in a Chinese family Singapore Medical Journal atypical splice mutation autosomal dominant polycystic kidney disease genetic test pkd genes |
| title | A new atypical splice mutation in PKD2 leading to autosomal dominant polycystic kidney disease in a Chinese family |
| title_full | A new atypical splice mutation in PKD2 leading to autosomal dominant polycystic kidney disease in a Chinese family |
| title_fullStr | A new atypical splice mutation in PKD2 leading to autosomal dominant polycystic kidney disease in a Chinese family |
| title_full_unstemmed | A new atypical splice mutation in PKD2 leading to autosomal dominant polycystic kidney disease in a Chinese family |
| title_short | A new atypical splice mutation in PKD2 leading to autosomal dominant polycystic kidney disease in a Chinese family |
| title_sort | new atypical splice mutation in pkd2 leading to autosomal dominant polycystic kidney disease in a chinese family |
| topic | atypical splice mutation autosomal dominant polycystic kidney disease genetic test pkd genes |
| url | https://journals.lww.com/10.11622/smedj.2021162 |
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