Scientists identify mutation that causes skin hyperproliferation

October 18, 2012

Scientists have identified a mutation in a gene that causes patches of very thick skin to appear on the palms and soles of affected people. This skin disorder is related, albeit in a much milder form, to that of the Indonesian 'Tree Man', Dede Koswara. These thick rough skin patches on hands and feet steadily increase in number as a person ages and often coalesce to form larger lesions. In severe cases, these lesions can be painful and debilitating.

The team of scientists from A*STAR's Institute of Medical Biology (IMB), in collaboration with hospitals and research centres from the UK, Japan and Tunisia, found that this , called punctate palmoplantar keratoderma (punctate PPK), is caused by mutations in the AAGAB gene. Punctate PPK is a rare subtype of palmoplantar keratoderma (PPK), which appears in subtly different forms and seems to have several possible causes. Several families in Singapore are afflicted by different types of PPKs and scientists at A*STAR have also been working with doctors at the National Skin Centre to understand the different forms of this skin disorder.

The identification of the will help scientists to better understand the molecular basis of this disease and potentially lead to a suitable treatment. This discovery will improve the classification and diagnosis of PPKs as well as open the door to novel approaches to treatment of skin disorders. These findings were published in the recent advanced online issue of on 14th October.

The scientists analyzed collected from 18 families from Scotland, Ireland, Japan and Tunisia who had punctate PPK. They showed that the AAGAB gene, which encodes the protein p34, was expressed in skin and had a role in the control of cell division. The depletion in AAGAB led to a deficiency in p34, which resulted in increased cell proliferation in the outer layers of skin, the epidermis, because of an increased growth signal coming through the epidermal growth factor receptor (EGFR). The disruption of EGFR signalling is a feature of abnormal and the discovery suggests that PPK may be a benign form of hyperproliferation.

Dr Bruno Reversade, Senior Principal Investigator at IMB, who is a member of the team said, "The study of rare genetic disorders can often provide unexpected links; the phenotype seen in punctate PPK patients bears striking resemblance to common warts, and it is tempting to speculate that HPV could also hijack the same pathways to induce skin hyperproliferation. This discovery also demonstrates that EGFR, a hallmark of skin cancer, is part of the molecular explanation of the overproliferation of lesions in PKK patients."

"Every time we find a new genetic mutation that causes a disorder, it helps patients and their families to demystify their condition," said Prof Birgitte Lane, Executive Director of IMB. "With scientists and doctors working towards common goals like this, we find better treatments for more and more of these rare conditions."

Explore further: New approaches may prevent certain side effects in BRAF mutation-positive melanoma

More information: Pohler, E. et al. Haploinsufficiency for AAGAB causes clinically heterogeneous forms of punctuate palmoplantar keratoderma, Nature Genetics. www.nature.com/ng/journal/vaop … nt/full/ng.2444.html

Related Stories

New approaches may prevent certain side effects in BRAF mutation-positive melanoma

November 13, 2011
Findings from preclinical studies in a skin cancer model showed that next-generation BRAF inhibitors used alone, or first-generation BRAF inhibitors used in combination with an epidermal growth factor receptor inhibitor, ...

First gene linked to common form of psoriasis identified

April 19, 2012
Scientists led by Washington University School of Medicine in St. Louis have identified the first gene directly linked to the most common form of psoriasis, a chronic skin condition.

Mutation linked with the absence of fingerprints

August 4, 2011
Scientists have identified a mutation that might underlie an extremely rare condition, called "adermatoglyphia," which causes people to be born without any fingerprints. The research, published by Cell Press online August ...

Groundbreaking discovery of mutation causing genetic disorder in humans

May 14, 2012
Scientists at A*STAR’s Institute of Medical Biology (IMB), in collaboration with doctors and scientists in Jordan, Turkey, Switzerland and USA, have identified the genetic cause of a birth defect known as Hamamy syndrome. ...

New research on gene mutation responsible for deafness shows it also causes heightened skin sensitivity

November 21, 2011
(Medical Xpress) -- Researchers have known since 1997 that mutations in the KCQN4 channel (a pathway that leads from the external environment to neurons) lead to progressive deafness and that the KCQN4 channel is only found ...

Recommended for you

Large genetic study links tendency to undervalue future rewards with ADHD, obesity

December 11, 2017
Researchers at University of California San Diego School of Medicine have found a genetic signature for delay discounting—the tendency to undervalue future rewards—that overlaps with attention-deficit/hyperactivity disorder ...

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.

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.