A new mutation in kidney disease

June 14, 2017
A new mutation in kidney disease
Figure 1. Predicted 3D structure of the novel mutant MUC1 protein. Credit: Yamamoto et al., Nephrology Dialysis Transplantation (2017), doi: 10.1093/ndt/gfx083

Medullary cystic kidney disease type 1 (MCKD1) is a rare genetic kidney disease. Despite this, because it is an autosomal dominant disease, once the mutation is in a family, many family members are affected. Current diagnostic methods discover the disease late in its development. Osaka University researchers studied one family in which 9 of 26 members were positive for MCKD1 and found a new mutation in the MUC1 gene that may act as an early marker of the disease.

"Besides and genetic testing, there is little we have to identify the ," says Associate Professor Jun-Ya Kaimori, a nephrologist at Osaka University Hospital. "There are very few early signs that show illness."

At the point of renal failure, patients are usually left with only extreme and invasive treatment options, such as dialysis or transplantation.

"MCKD1 is caused by a single mutation in MUC1 gene discovered in 2013," he continued.

The mutation is located in a region of the gene that includes GC-rich variable number of tandem repeats (VNTR). This, explains Kaimori, makes it very difficult to analyze.

"The standard technique to analyze is next-generation sequencing. VNTR have a tertiary structure that makes it very difficult to analyze by . Even finding the mutation took immense time and effort," he said.

In his latest research study, Kaimori and his colleagues used whole-exome sequencing to analyze the gene and found a second mutation outside the VNTR.

"The mutation was a deletion of just two base pairs, but that was enough to change the protein structure."

A new mutation in kidney disease
Figure 2. Localization change of the mutant MUC1 protein. Credit: Yamamoto et al., Nephrology Dialysis Transplantation (2017), doi: 10.1093/ndt/gfx083

The original MUC1 mutation was found by a collaboration of scientists from U.S. and European institutes. When asked why his group found the mutation but the international collaboration did not, Kaimori frankly replied, "It was an unexpected discovery."

Unlike the first mutation, the location of the new mutation allowed the scientists to study the effects of the mutated protein further. Experiments suggested that the mutation disrupts the function of MUC1 and changes its location inside cells. This last observation excited Kaimori, because it suggested a potential biomarker to diagnose patients before renal failure.

"We found patients had high levels of mutant MUC1 in urinary exosomes, but healthy people had normal MUC1 in urinary exosomes. These results suggest we can use urinary exosomes for non-genetic testing to evaluate the risk of MCKD1."

Explore further: Kidney disease mutations found in a genomic blind spot

More information: Satoko Yamamoto et al. Analysis of an ADTKD family with a novel frameshift mutation in MUC1 reveals characteristic features of mutant MUC1 protein, Nephrology Dialysis Transplantation (2017). DOI: 10.1093/ndt/gfx083

Related Stories

Kidney disease mutations found in a genomic blind spot

February 11, 2013
(Medical Xpress)—Advances in DNA sequencing technology during the past decade have given scientists powerful tools to peer into the genomes of humans and other species. Despite the efficiency and sophistication of these ...

Mutation linked to congenital urinary tract defects

July 17, 2013
Researchers at Columbia University Medical Center (CUMC) and collaborators have identified a genetic mutation that causes congenital malformations of the kidney and urinary tract, a common form of birth defect and the most ...

Rare feline genetic disorders identified through whole genome sequencing

May 11, 2017
Whole genome sequencing (WGS), which is the process of determining an organism's complete DNA sequence, can be used to identify DNA anomalies that cause disease. Identifying disease-causing DNA abnormalities allows clinicians ...

Scientists show how mutation causes incurable premature aging disease

October 31, 2016
Scientists have demonstrated how a mutation in a specific protein in stem cells causes an incurable premature aging disease called dyskeratosis congenita, and were able to introduce the mutation into cultured human cells ...

Parkinson's gene linked to lung cancer

January 29, 2015
Researchers at the Medical College of Wisconsin (MCW), in collaboration with other colleagues of the Genetic Epidemiology of Lung Cancer Consortium (GELCC), have identified a gene that is associated with lung cancer.

Researchers find association between gene mutation and rare heart disease

November 15, 2016
A strong association between a genetic mutation and a rare kind of heart muscle disease has been discovered by researchers at the University of Colorado Anschutz Medical Campus.

Recommended for you

Gene variants identified that may influence sexual orientation in men and boys

December 8, 2017
(Medical Xpress)—A large team of researchers from several institutions in the U.S. and one each from Australia and the U.K. has found two gene variants that appear to be more prevalent in gay men than straight men, adding ...

Disease caused by reduction of most abundant cellular protein identified

December 8, 2017
An international team of scientists and doctors has identified a new disease that results in low levels of a common protein found inside our cells.

Study finds genetic mutation causes 'vicious cycle' in most common form of amyotrophic lateral sclerosis

December 8, 2017
University of Michigan-led research brings scientists one step closer to understanding the development of neurodegenerative disorders such as ALS.

Mutations in neurons accumulate as we age: The process may explain normal cognitive decline and neurodegeneration

December 7, 2017
Scientists have wondered whether somatic (non-inherited) mutations play a role in aging and brain degeneration, but until recently there was no good technology to test this idea. A study published online today in Science, ...

Researchers find genes may 'snowball' obesity

December 7, 2017
There are nine genes that make you gain more weight if you already have a high body mass index, McMaster University researchers have found.

Gene therapy shows promise against blood-clotting disease

December 7, 2017
Gene therapy has freed 10 men from nearly all symptoms of hemophilia for a year so far, in a study that fuels hopes that a one-time treatment can give long-lasting help and perhaps even cure the blood disease.

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.