A study has found that flat pigmentation disease is caused by an increased incidence of pigmented newborns and is caused primarily by mutations in the melanocortin receptor gene, a gene linked to melanin production.
The findings, published in the American Journal of Medical Genetics Part B, will be presented to the European Society of Pediatric Dermatology at the Society for Pediatric Genetics, in Amsterdam, on April 27.
The study, published April 27 in the journal Dermatologic Genetics, is the first to describe an increased risk of flat pigments in newborns with the gene mutation, which is located on chromosome 11, the third of 13 known gene variants that affect the skin pigments and pigmentation of the skin.
The mutation, first discovered in 2003, is associated with several skin pigment disorders.
Researchers have found that mutations in melanocollin, a protein found on the surface of cells, have been associated with pigmentation disorders such as paler skin, brown eyes, and flat pigment syndrome, which has been linked to the common birthmark phenomenon known as flat pigming.
A genetic analysis of a group of infants showed that more than half of them had an increase in melanin levels, and almost two-thirds of them also had a decrease in the levels of the gene.
“In our study, we found that the melanin in the skin is increased in infants with the mutation,” said lead author Andrea M. P. Zavala, M.D., an assistant professor of dermatology at The Johns Hopkins University School of Medicine.
“We are trying to determine if this gene mutation can be associated with these skin pigmented disorders.”
In addition to identifying the gene variant, the researchers also found that a second mutation, called MC3R, has been associated also with flat piging, but this is a rare condition and has been identified only in children and adolescents.
In this study, they identified two other gene mutations that could increase the risk of the condition.
“There are a number of genes in our genome that affect our skin,” said Zavalya.
“The melanocordin receptor is one of them.
The melanocoronin receptor plays a role in the production of melanin.”
These two genes also affect the production and function of melanosomes, or pigments, which help produce the pigment pigment in the epidermis.
“These pigments are what give skin its natural color,” said P.T. Wahlstedt, M.-D., Ph.
D. an associate professor of molecular and cellular biology at the University of Illinois at Urbana-Champaign and the senior author of the study.
“Our work suggests that if we can figure out how to change these genes, we could perhaps reduce the risk for some of these disorders.”
The researchers found that there were four mutations in MC3L and MC3S that increased the risk.
Of these, MC3A1 was the most significant.
MC3B1, MC2C, MC4R and MC2D are mutations in both the melanocyte-derived suppressor gene, which codes for the melanogen receptor, and the melanosome-dependent protein, which makes the pigment in pigmented skin piglets.
The researchers also discovered that mutations of MC4A1 and MC4B1 were associated with flat pigment syndrome.
“It was clear that the mutation in MC4a1 was associated with the flat pigring in the infant,” said M.C. Zavanac, MSc., associate professor and senior author.
“This mutation is very common in the general population and affects between one in five and one in ten infants in Europe.
In our study we found it in nearly three-quarters of the children with this condition.
This suggests that this mutation is also present in a minority of infants.”
The team also identified two additional gene mutations related to flat pigting, and these were found to be associated to other conditions as well.
“Two of these mutations have been identified in the European population but have not been identified previously,” said Wahlstadt.
“And they also were found in one of the infants with this disease, which suggests that it is the same mutation that affects both cases.
It is not clear how these other two mutations affect the risk.”
These gene mutations were first identified in humans by Dr. S.A. Raghavan in 2005.
In 2012, the research team, which included researchers from the University Hospital of Antwerp, the University Medical Center, and Leiden University Medical School, published a study that identified a similar mutation in a human in another disorder called the “flat pigment syndrome.”
In that case, the mutation was associated not only with pigmented neonates but also with the other skin pigings in the infants.
The team used DNA sequencing technology to map the genetic structure of these two mutations and found that they are related to the same gene