Scientists identify genetic cause of 'spongy' skin condition

July 03, 2013

Scientists have identified the genetic cause of a rare skin condition that causes the hands and feet to turn white and spongy when exposed to water.

The study, led by researchers from Queen Mary, University of London, has provided scientists with an insight into how the skin barrier functions and could help with research into a variety of conditions.

Diffuse non-epidermolytic palmoplantar keratoderma (NEPPK) is a rare condition in which individuals have thickened, yellowish skin over their palms and soles, thickened nails and suffer from excessive sweating. When their hands and feet are exposed to water, the skin quickly turns white and spongy and individuals are prone to fungal infections.

While prevalence in the general population is estimated at one in 40,000 it is much higher in northern Sweden (up to one in 200 people)*, where a single ancestral genetic mutation is believed to have originated and then subsequently passed down from generation to generation.

A team led by David Kelsell, Professor of Human Molecular Genetics at Queen Mary studied DNA from a number of families of British and Swedish origin in which the skin condition is present. Using high throughput DNA sequencing methods they were able to pin down the underlying cause of the condition to mutations in the AQP5 gene, which encodes a water channel protein known as aquaporin 5. All individuals who have inherited an AQP5 mutation will present with this rare skin condition.

Professor Kelsell, from the Blizard Institute at Barts and The London School of Medicine and Dentistry, Queen Mary, said: "Aquaporins are a family of proteins known as "the plumbing system for cells" as they form pores which allow water to flow through cells rapidly.

"We knew aquaporin 5 was present in high amounts in the sweat glands, salivary glands and tear ducts -- routes by which the body loses water. Here we've demonstrated it is also found in the skin, with higher amounts in the hands and feet."

Co-author Dr Diana Blaydon, also from the Blizard Institute, explained: "The AQP5 gene mutation appears to result in a protein that has a wider channel than usual, forming a bigger pore in the cell membrane allowing more water to permeate it."

Further work is needed to understand exactly how the mutations identified and the associated changes in the skin barrier lead to NEPPK.

Professor Kelsell added: "While we've studied aquaporins in the skin, these results also give us an idea of what might be happening in internal aquaporins, which are found in structures throughout the body, including the kidneys, cornea and lungs."
-end-
*Figures from orpha.net

Queen Mary University of London

Related Mutations Articles from Brightsurf:

SARS-CoV-2 mutations do not appear to increase transmissibility
None of the mutations currently documented in the SARS-CoV-2 virus appear to increase its transmissibility in humans, according to a study led by UCL researchers, published in Nature Communications.

Predicting the evolution of genetic mutations
CSHL quantitative biologists have designed a new machine learning technique for predicting evolutionary pathways.

SNIPRs take aim at disease-related mutations
In a new study, lead author Alex Green, a researcher at the Biodesign Center for Molecular Design and Biomimetics and his colleagues describe a new method for detecting point mutations.

Cancer mutations occur decades before diagnosis
A large-scale pan-cancer analysis of the evolutionary history of tumours reveals that cancer-causing mutations occur decades before diagnosis.

Pinpointing rare disease mutations
Scientists have compiled mouse and human cell knockout data to categorise genes based on how essential they are for survival and organism development.

Using deep learning to predict disease-associated mutations
A research team led by Professor Hongzhe Sun from the Department of Chemistry at HKU, implemented a robust deep learning approach to predict disease-associated mutations of the metal-binding sites in a protein.

Cancer: The origin of genetic mutations
In the presence of some disruptive elements, cancer cells are unable to replicate its DNA optimally.

Mutations associated with sensitivity or resistance to immunotherapy in mNSCLC
The relationship between gene alterations and response to anti-PD-L1 with and without anti-CTLA-4 are not well characterized.

Machine learning for damaging mutations prediction
Scientists from Russia and India have proposed a novel machine-learning-based method for predicting damaging mutations in the protein atomic structure.

Discovery of new mutations may lead to better treatment
In the largest study to date on developmental delay, researchers analyzed genomic data from over 31,000 parent-child trios and found more than 45,000 de novo mutations, and 40 novel genes.

Read More: Mutations News and Mutations Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.