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A Presumed Synonymous Mutation of PKD2 Caused Autosomal Dominant Polycystic Kidney Disease in a Chinese Family

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Abstract

Objective

Autosomal dominant polycystic kidney disease (ADPKD) is mainly caused by the pathogenic mutation of PKD1 or PKD2 gene and usually affects bilateral kidneys. Synonymous mutations are generally assumed to be neutral as they do not alter amino acids. Herein, we described an extremely rare ADPKD child caused by a heterozygous synonymous mutation of PKD2 gene accompanied by massive proteinuria and congenital solitary kidney.

Methods

Clinical characteristics of the patients were summarized. Whole-exome sequencing was performed to screen the disease-causing gene mutation, and reverse transcription polymerase chain reaction (RT-PCR) and Sanger sequencing were applied to analyze the impact of the identified mutation on gene transcription and splicing.

Results

Polycystic changes were found in the solitary kidney of a girl initially presented with nephrotic-range proteinuria. Thereafter her mother and 2 other family members were diagnosed to be ADPKD. Whole-exome sequencing of the proband identified a heterozygous synonymous mutation (c.1716G>A, p.Lys572=) located in the splicing site of exon 7 in PKD2 gene, which was co-segregated with the PKD phenotype in the family. RT-PCR and direct sequencing of amplified products revealed that this heterozygous synonymous mutation led to exon7 skipping in PKD2 gene.

Conclusion

We reported an extremely rare child case of ADPKD2 in combination with solitary kidney and nephrotic-range proteinuria, and firstly confirmed the pathogenicity of a heterozygous synonymous mutation (c.1716G>A) in PKD2 gene. The results indicate that synonymous mutations should not be excluded from disease-causing if they are located in splicing site of an exon.

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Authors and Affiliations

  1. Department of Pediatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China

    Lin-xia Deng, Yuan Yang, Jing Yang & Jian-hua Zhou

  2. Department of Neurosurgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China

    Luo-wen Zhou

  3. Department of Forensic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China

    Kang Wang

Authors
  1. Lin-xia Deng
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  2. Yuan Yang
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  3. Jing Yang
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  4. Luo-wen Zhou
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  5. Kang Wang
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  6. Jian-hua Zhou
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Corresponding author

Correspondence to Jian-hua Zhou.

Additional information

This work was supported by the National Natural Science Foundation of China (No. 81873596).

Conflict of Interest Statement

The authors declare that they have no competing interests.

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Deng, Lx., Yang, Y., Yang, J. et al. A Presumed Synonymous Mutation of PKD2 Caused Autosomal Dominant Polycystic Kidney Disease in a Chinese Family. CURR MED SCI 41, 1029–1036 (2021). https://doi.org/10.1007/s11596-021-2436-9

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  • DOI: https://doi.org/10.1007/s11596-021-2436-9

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