|Researchers Discover Gene For Rare Skin Disorder
Researchers funded in part by the National Institutes of Health
have identified the gene that accounts for most cases of Goltz
syndrome, a rare skin disorder that can also affect bone and eye
The cases appear to result from a defect in the gene known as
PORCN, which contains the information needed to make a protein,
referred to by researchers as porcupine. The Porcupine protein,
which was first identified in fruit flies, was named for the pattern
of spikes projecting from skin cells of the larval fly’s body,
bearing a resemblance to the quills of a porcupine.
The researchers believe mutations in the PORCN gene cause at least
75 percent of Goltz syndrome cases.
“Identifying a genetic mutation for Goltz syndrome is a critical
first step in understanding and eventually treating the condition,” said
Duane Alexander, director of the National Institute of Child Health
and Human Development, the NIH institute that provided funding
for the Mental Retardation and Developmental Disabilities Research
Center at Baylor College of Medicine, where the study was conducted.
The study was lead jointly by Xiaoling Wang, Department of Obstetrics
and Gynecology at Baylor College of Medicine, and V. Reid Sutton,
Department of Molecular and Human Genetics at Baylor College of
The findings were published online in Nature Genetics.
Goltz syndrome, also called focal dermal hypoplasia, causes a
distinctive red rash and thinning of the skin, which allows fat
from the tissue below to protrude and form small yellowish-white
The disorder often causes brittle hair and nails, and deformities
in the hands, such as extra, missing, or deformed fingers. Individuals
with Goltz syndrome can also have missing or underdeveloped eyes.
In addition, the disorder can affect the stomach, intestines, heart,
lungs, and kidneys, said Dr. Ignatia B. Van den Veyver, associate
professor at Baylor College of Medicine’s Departments of Obstetrics
and Gynecology and of Molecular and Human Genetics and the senior
author of the paper. Mental retardation is seen in about fifteen
percent of patients with Goltz syndrome.
Because 90 percent of Goltz syndrome cases are seen in females,
the disorder was believed to be caused by a gene on the X chromosome.
After analyzing the genes of two girls with Goltz syndrome, the
researchers found that both patients were missing a portion of
the X chromosome where seven genes are located. Of the missing
seven, the researchers learned that Goltz syndrome resulted from
an absence of the PORCN gene, said Dr. Van den Veyver.
The PORCN gene is active in the embryo and fetus, creating proteins
important in the development of the skin, skeleton, and eyes — all
affected in the disorder.
Researchers then did genetic analyses of 15 girls with Goltz syndrome
and found that the PORCN gene was affected in 10 of them.
Although the PORCN gene has been studied in mice and fruit flies,
very little is known about the gene’s function in humans, said
Dr. Van den Veyver. The mouse and Drosophila porcupine proteins
are known to be important for the secretion of Wnt proteins from
the cells that produce them. Wnt proteins are involved in early
development. They interact with other proteins within the cell
to begin the complex chain of events leading to the development
and differentiation of organ systems in early life.
This discovery may lead to greater understanding of the function
of Wnt proteins in humans, said Dr. Van den Veyver.
By identifying the genetic defect which causes Goltz syndrome,
it may be possible to understand more of the processes critical
for skin, eye and bone development, she said.
“The findings are important because they offer insight into a
developmental disorder that was previously little understood,” said
Ljubisa Vitkovic, M.D., of NICHD’s Mental Retardation and Developmental
Disabilities Branch. “But they also illustrate how a mutation in
the human counterpart of a protein known to regulate development
in flies and mice can affect the skin and other human organs.”
The NICHD sponsors research on development, before and after birth;
maternal, child, and family health; reproductive biology and population
issues; and medical rehabilitation. For more information, visit
the Institute’s Web site at http://www.nichd.nih.gov.
The National Institutes of Health (NIH) — The Nation's
Medical Research Agency — includes 27 Institutes and
Centers and is a component of the U.S. Department of Health and
Human Services. It is the primary federal agency for conducting
and supporting basic, clinical and translational medical research,
and it investigates the causes, treatments, and cures for both
common and rare diseases. For more information about NIH and
its programs, visit www.nih.gov.