Featured Research

from universities, journals, and other organizations

Mutations Identified In Gene Causing Blindness, Early Heart Attacks

Date:
May 16, 2000
Source:
Jefferson Medical College
Summary:
Molecular geneticists at Jefferson Medical College have for the first time characterized gene mutations in families affected by a rare, inherited, connective tissue disorder that can lead to blindness and early heart attacks. The work provides the basis for DNA-based carrier detection, prenatal testing and a better understanding of the mechanisms behind the disease, known as pseudoxanthoma elasticum (PXE).

The findings may lead to improved diagnosis for a rare connective tissue disease

Molecular geneticists at Jefferson Medical College have for the first time characterized gene mutations in families affected by a rare, inherited, connective tissue disorder that can lead to blindness and early heart attacks. The work provides the basis for DNA-based carrier detection, prenatal testing and a better understanding of the mechanisms behind the disease, known as pseudoxanthoma elasticum (PXE).

PXE is difficult to diagnose because the symptoms don’t often show up until the teens or early 20s. Typically, the affected person appears to have severely sun-damaged skin. But the symptoms belie a much more dangerous condition, which, if unchecked, can lead to progressive loss of vision, gastrointestinal bleeding and cardiovascular disease, including poor circulation and early heart attacks.

Jouni Uitto, M.D, PhD, professor and chair of dermatology and cutaneous biology and Franziska Ringpfeil, MD, a dermatology resident, both of Jefferson Medical College of Thomas Jefferson University in Philadelphia, and their co-workers at Jefferson and at the Mt. Sinai School of Medicine in New York studied eight families in which 13 members with the disorder had a damaged gene, MRP6, on chromosome 16. They characterized each person’s mutation type and compared the affected individuals’ physical condition and genetics with that of 20 unaffected family members. The researchers also identified several carriers of the PXE trait in unaffected individuals.

Dr. Uitto and his colleagues report their findings May 23 in the Proceedings of the National Academy of Sciences.

"These findings allow us now to provide accurate diagnosis and carrier detection within the family using a simple blood test," says Dr. Uitto, who is also director of the Jefferson Institute of Molecular Medicine. "We can look at children of affected individuals and do presymptomatic testing. If the families want, we can also perform prenatal testing." Jefferson’s Molecular Diagnostics Laboratory, he notes, is an international center for diagnosing another devastating inherited disorder, epidermylosis bullosa, a painful skin blistering disease.

"This is the first gene to be identified as having mutations causing or at least contributing to the disease," he says. The mutation has several variations. In some cases, the gene’s protein is altered and doesn’t work; in others, an entire gene copy is missing.

According to Dr. Uitto, the MRP6 gene belongs to a family of genes that may make a protein that serves as a molecular pump as part of an internal detoxification mechanism. "No one knows exactly what MRP6 does, but it is primarily expressed by the kidney and liver," he says. If the gene is damaged and not working properly, he speculates, "some compounds may accumulate in the blood that have an affinity for elastic structure in various organs. This binds to elastin and calcium, resulting in progressive calcification. It would also explain the delayed onset of the disease, since the accumulation would take time."

PXE is relatively rare, with estimates ranging from one in 25,000 to 50,000 affected in the general population. Most cases are autosomal recessive, meaning if two faulty gene carriers have children, there is a one in four chance of the child having the disease.

PXE is diagnosed by skin lesions as well as the presence of angioid streaks, which are abnormalities in the back of the eye, and which can lead to blindness. Circulation problems from the disorder can lead to early heart attacks.

Dr. Uitto suggests that reducing calcium intake and avoiding cigarette smoking may help slow disease progression. Those with a family history of the disease should have regular eye examinations to head off possible problems. Plastic surgery is an option to remove excess sagging skin.

His group would next like to study additional PXE families to try to better understand how the damaged gene is inherited. "We would also like to understand the function of the gene and its protein and be able to find out if other genes are involved as well," he says. A key to really understanding the gene’s function, he says, is to create a "knockout" mouse lacking the gene, enabling the scientists to see what the specific effects are of a missing gene and protein.

"Such animals would also provide a means to test novel treatment modalities, including gene therapy, for this progressive and often devastating disease," Dr. Uitto says.


Story Source:

The above story is based on materials provided by Jefferson Medical College. Note: Materials may be edited for content and length.


Cite This Page:

Jefferson Medical College. "Mutations Identified In Gene Causing Blindness, Early Heart Attacks." ScienceDaily. ScienceDaily, 16 May 2000. <www.sciencedaily.com/releases/2000/05/000516072529.htm>.
Jefferson Medical College. (2000, May 16). Mutations Identified In Gene Causing Blindness, Early Heart Attacks. ScienceDaily. Retrieved July 23, 2014 from www.sciencedaily.com/releases/2000/05/000516072529.htm
Jefferson Medical College. "Mutations Identified In Gene Causing Blindness, Early Heart Attacks." ScienceDaily. www.sciencedaily.com/releases/2000/05/000516072529.htm (accessed July 23, 2014).

Share This




More Health & Medicine News

Wednesday, July 23, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Courts Conflicted Over Healthcare Law

Courts Conflicted Over Healthcare Law

AP (July 22, 2014) Two federal appeals courts issued conflicting rulings Tuesday on the legality of the federally-run healthcare exchange that operates in 36 states. (July 22) Video provided by AP
Powered by NewsLook.com
Why Do People Believe We Only Use 10 Percent Of Our Brains?

Why Do People Believe We Only Use 10 Percent Of Our Brains?

Newsy (July 22, 2014) The new sci-fi thriller "Lucy" is making people question whether we really use all our brainpower. But, as scientists have insisted for years, we do. Video provided by Newsy
Powered by NewsLook.com
Scientists Find New Way To Make Human Platelets

Scientists Find New Way To Make Human Platelets

Newsy (July 22, 2014) Boston scientists have discovered a new way to create fully functioning human platelets using a bioreactor and human stem cells. Video provided by Newsy
Powered by NewsLook.com
Gilead's $1000-a-Pill Drug Could Cure Hep C in HIV-Positive People

Gilead's $1000-a-Pill Drug Could Cure Hep C in HIV-Positive People

TheStreet (July 21, 2014) New research shows Gilead Science's drug Sovaldi helps in curing hepatitis C in those who suffer from HIV. In a medical study, the combination of Gilead's Hep C drug with anti-viral drug Ribavirin cured 76% of HIV-positive patients suffering from the most common hepatitis C strain. Hepatitis C and related complications have been a top cause of death in HIV-positive patients. Typical medication used to treat the disease, including interferon proteins, tended to react badly with HIV drugs. However, Sovaldi's %1,000-a-pill price tag could limit the number of patients able to access the treatment. TheStreet's Keris Lahiff reports from New York. Video provided by TheStreet
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:
from the past week

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins