Genetic mutation associated with a rare skin disease identified

A study co-led by Torunn Fiskerstrand at Haukeland University Hospital in Norway and Michele Ramsay at the University of the Witwatersrand in South Africa has revealed genetic mutation responsible for an common skin disease known as keratolytic winter erythema (KWE).

KWE is also known as Oudtshoorn skin and Erythrokeratolysis hiemalis ichthyosis. Typical symptoms include cyclical erythema, hyperkeratosis, and peeling of the skin of the palms and soles. The condition is worse in the winter. KWE is quite prevalent among the South African Afrikaans-speaking Caucasoid population. According to estimates, its prevalence in this population is about 1/7200. Initially KWE was believed to be unique to South Africa, but recent studies have shown that individuals in other countries may also develop the disease.

KWE has been mapped to human chromosome 8p22-p23. This region is the so-called KWE critical region. Additionally, loss of heterozygosity of chromosome 8p has been found in a variety of cancers such as breast cancer, hepatocellular carcinoma, intrahepatic cholangiocarcinoma, and urinary bladder cancer.

Until now, the cause of KWE is incompletely understood. The identification of the gene causing KWE will extend the understanding of the disease pathogensis. Fiskerstrand, Ramsay, and their team set out to study the genetic underpinning of KWE.

The study enrolled five South African families and two Norwegian families. Using targeted resequencing and whole-genome sequencing techniques, the researchers identified two overlapping tandem duplications of 7.67 kb (South Africans) and 15.93 kb (Norwegians). Further investigation demonstrated that the mutation causes a nearby gene called CTSB to produce more protein than normal and the up-regulation of CTSB seems to be the cause of the skin peeling.

The CTSB gene encodes cathepsin B, a cysteine protease that plays an important role in intracellular proteolysis. Overexpression of cathepsin B has been associated with many tumors. (cathepsin B and other proteins like Recombinant AGTR1 can be offered by Cusabio.)

Published April 27, 2017 in The American Journal of Human Genetics, this study will lead to a deeper understanding of KWE. In addition to Haukeland University Hospital and University of the Witwatersrand, the study also involves researchers from Radboud University, Oslo University Hospital, Pfizer Worldwide R&D, Novartis Institutes for BioMedical Research, University of Bergen, Radboud University Medical Center, Tufts University School of Medicine, Dalhousie University, Bristol-Myers Squibb, and Radboud University.