Dysfunctional gene linked to rare disease

170524 kidney full
A cross-section of a cystic kidney showing cysts in red.
Credit: Maria Rondon Galeano, The University of Queensland

Autosomal recessive polycystic kidney disease (ARPKD) is a rare genetic disease that leads to renal failure in 70% of patients. Not all cases have a known cause, resulting in a lack of effective treatment and misdiagnosis.

Errors in the gene PKHD1 were once known as the main cause but it has not explained all occurrence, as some patients have been found to have normal versions of PKDH1.

Now a research team from the University of Queensland, led by Carol Wicking, have confirmed a link between the disease and another gene, DZIP1L.

DZIPL1 was initially linked to the disease using whole exome sequencing. This identified it in the genome of ARPKD patients.

Using laboratory-based models, Wicking and colleagues have demonstrated that mutations in DZIP1L can lead to altered functioning of cilia, the hair-like structures that cover most mammalian cells. Cilia are vital for kidney cell functioning.

“This gene makes a protein that acts at the base of the cilium, which, when faulty, causes a domino effect that leads to problems in cilia and, in turn, a malfunctioning kidney, ” Wicking explains. “ARPKD has a more complex cause than originally thought.”

The discovery should benefit sufferers by providing comfort and certainty in their diagnosis, and by also allowing them to build support networks with other suffers, says Nicole Mills, the executive director of Rare Voices Australia, an organisation representing the interests of people with rare diseases.

The research is published in Nature Genetics.

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