DNA strand intertwined with a kidney

A Genetic Twist: Unraveling Polycystic Kidney Disease in a Chinese Family

Samir D’Costa in Health & Wellness August 2025 • 4 min read.

"Scientists identify a novel gene mutation offering new insights into autosomal dominant polycystic kidney disease (ADPKD)."

Autosomal dominant polycystic kidney disease (ADPKD) is a common inherited disorder that affects approximately 1 in 400 to 1000 individuals. This condition is characterized by the development of numerous cysts in the kidneys, which can eventually lead to kidney failure. Understanding the genetic basis of ADPKD is crucial for improving diagnosis and potentially developing targeted therapies.

Two genes, PKD1 and PKD2, are primarily responsible for ADPKD. Mutations in PKD1 account for about 85% of cases, while PKD2 mutations are responsible for the remaining 15%. These genes produce proteins called polycystin-1 and polycystin-2, respectively, which play critical roles in maintaining the normal structure and function of kidney tubules.

Now, a recent study has uncovered a novel splicing mutation in the PKD1 gene within a Chinese family affected by ADPKD. This discovery not only expands our knowledge of the genetic landscape of ADPKD but also offers valuable insights into the mechanisms driving the disease.

Decoding the PKD1 Mutation: A Genetic Investigation

The study involved a detailed genetic analysis of a Chinese family with a history of ADPKD. Researchers extracted DNA samples from affected family members and performed targeted next-generation sequencing to analyze genes associated with kidney diseases. This approach allowed them to identify a specific mutation within the PKD1 gene.

The identified mutation, c.2854-3C > G (also known as IVS11–3C > G), is a splicing mutation. Splicing mutations affect how genetic information is processed, potentially leading to abnormal protein production. This particular mutation was found in all three affected individuals in the family but was absent in unaffected relatives and a control group of 100 individuals.

Next-Generation Sequencing: Employed to analyze renal disease-related genes.
Splicing Mutation: Identified as c.2854-3C > G in the PKD1 gene.
Family Specific: Present in affected individuals, absent in unaffected relatives and controls.

To understand the impact of this mutation on the gene's function, the researchers performed reverse transcription-PCR (RT-PCR) to analyze mRNA expression in patient samples. mRNA sequencing revealed that the mutation caused 29 extra bases to be inserted into the 3'-end of exon 11 of the PKD1 gene. This insertion leads to a frameshift mutation, disrupting the normal reading frame of the genetic code.

Implications and Future Directions

The discovery of the PKD1 c.2854-3C > G mutation provides new insights into the pathogenesis of ADPKD. This specific mutation leads to a frameshift during the translation of the polycystin-1 protein, ultimately resulting in a truncated, non-functional protein.

The truncated protein lacks essential domains required for proper cellular function, including signal transduction and regulation of gene transcription. This disruption contributes to abnormal kidney development and cyst formation, the hallmarks of ADPKD.

These findings have significant implications for the diagnosis and potential treatment of ADPKD. Identifying this novel mutation can improve genetic screening and counseling for families at risk. Further research is needed to explore the potential for targeted therapies that address the specific defects caused by this and other PKD1 mutations, offering hope for more effective interventions in the future.

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This article is based on research published under:

DOI-LINK: 10.1186/s12881-018-0706-6, Alternate LINK

Title: A Novel Splicing Mutation In The Pkd1 Gene Causes Autosomal Dominant Polycystic Kidney Disease In A Chinese Family: A Case Report

Subject: Genetics (clinical)

Journal: BMC Medical Genetics

Publisher: Springer Science and Business Media LLC

Authors: Peiwen Xu, Sexing Huang, Jie Li, Yang Zou, Ming Gao, Ranran Kang, Junhao Yan, Xuan Gao, Yuan Gao

Published: 2018-11-13

Everything You Need To Know

What is Autosomal dominant polycystic kidney disease (ADPKD)?

Autosomal dominant polycystic kidney disease (ADPKD) is an inherited disorder characterized by the development of numerous cysts in the kidneys, which can lead to kidney failure. It affects approximately 1 in 400 to 1000 individuals. This condition arises from mutations in the PKD1 and PKD2 genes. The identification of these genes and their roles is critical for understanding and managing the disease.

What are the roles of PKD1 and PKD2 genes?

The PKD1 gene provides instructions for making a protein called polycystin-1, and the PKD2 gene provides instructions for making a protein called polycystin-2. These proteins are essential for the normal structure and function of the kidney tubules. When mutations occur in these genes, it can disrupt the production of functional polycystin-1 and polycystin-2 proteins, leading to the formation of cysts and the development of ADPKD.

What is a splicing mutation, and what is its impact?

A splicing mutation, such as the c.2854-3C > G mutation in the PKD1 gene, affects the process of RNA splicing. Splicing is a critical step in gene expression where non-coding regions (introns) are removed from the pre-mRNA, and the coding regions (exons) are joined together. The identified mutation disrupts this process, causing 29 extra bases to be inserted into the mRNA. This insertion leads to a frameshift, ultimately producing a truncated, non-functional polycystin-1 protein.

What is next-generation sequencing, and how was it used in the study?

Next-generation sequencing (NGS) is a high-throughput method used to rapidly sequence large stretches of DNA. In this study, NGS was employed to analyze the genes associated with kidney diseases, allowing researchers to identify the specific mutation in the PKD1 gene within the affected Chinese family. This technique provides a detailed view of the genetic landscape and enables the identification of specific mutations related to ADPKD.

Why is the discovery of the PKD1 c.2854-3C > G mutation important?

The discovery of the PKD1 c.2854-3C > G mutation is significant because it provides new insights into the genetic mechanisms underlying ADPKD. This mutation leads to a non-functional polycystin-1 protein, which is likely a key factor in the development of cysts and kidney failure. Understanding the specific mutations and their effects on protein function is crucial for developing targeted therapies and improving diagnostics for ADPKD.