August 27, 2019
Keio University School of Medicine
National Center for Child Health and Development
Japan Agency for Medical Research and Development
A joint research group led by Associate Professor Akiharu Kubo of the Department of Dermatology, Keio University School of Medicine, and Dr. Kazuhiko Nakabayashi, Head of the Department of Maternal-Fetal and Neonatal Medicine at the National Center for Child Health and Development, has revealed that 1 in 400 Japanese people has a congenital predisposition to a skin disease called porokeratosis. Furthermore, they found that in such individuals, when the genome of skin cells undergoes acquired changes due to factors like ultraviolet radiation, multiple porokeratosis lesions develop all over the body.
Porokeratosis is a disease characterized by multiple, flat, slightly raised red or brown lesions (skin rashes) that are circular or annular in shape and several millimeters to several centimeters in diameter, appearing all over the body. It is known that skin cancer can easily develop from these lesions. Types of porokeratosis include "linear porokeratosis," where lesions are concentrated on one part of a child's body, and "disseminated superficial actinic porokeratosis," where lesions appear all over the body, mainly on the arms and legs, in adulthood.
It was known that individuals who develop porokeratosis have one congenital change (gene mutation) in a gene such as *MVD* or *MVK*. Since human cells have two copies of each gene, if one copy is altered and non-functional, the other acts as a spare, and typically no problems arise. The mechanism by which individuals with a change in only one copy of the gene develop porokeratosis was previously completely unknown.
This study revealed that: (1) approximately 1 in 400 Japanese people has a congenital change in the *MVD* gene and thus a predisposition to porokeratosis; (2) cells in which both copies of the *MVD* gene have become non-functional due to an acquired change in the genome (hereafter, a "second hit") form the skin lesions of porokeratosis; and (3) if a second hit occurs only once during the fetal period, it results in "linear porokeratosis," whereas if it occurs repeatedly in various places on adult skin, it results in "disseminated superficial actinic porokeratosis."
The findings of this research are expected to lead to the elucidation of the mechanism by which porokeratosis develops into skin cancer, as well as to the development of preventive and therapeutic methods for porokeratosis.
These research findings were published in the online edition of the "Journal of Investigative Dermatology," the academic journal of the Society for Investigative Dermatology, on August 26, 2019 (Greenwich Mean Time).
Please see below for the full press release.