Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

In 15 seconds, new test will ID presence of 25 most common mutations of cystic fibrosis

21.07.2003


"Eighty percent of all babies born in the US that have cystic fibrosis (CF) are born to parents with no previous family history." This attention-getting quote, used frequently by an activist in the CF community, makes it powerfully clear what few people realize: that both parents did not know they would pass on to their child the life-altering CFTR gene, the gene mutated in cystic fibrosis.



In fact, the Cystic Fibrosis Foundation estimates that more than 10 million Americans are unknowing, asymptomatic carriers of CF, which causes a thickening mucous to surround the lungs and serves as a catalyst for multiple, life-threatening infections throughout a lifetime.

Background


Approximately 30,000 children and adults in the US suffer from CF. In the Caucasian population, where it is most prevalent, one in 30 white Americans carry the mutated gene in their genome but do not manifest the disease. When one carrier with a certain disease allele mates with another who carries the identical disease allele, a process of recombination produces an offspring with the double mutation necessary to cause the disease. One in 3,000 live births has CF today.

CF has more than 1,000 currently known mutations and additional mutations are being discovered regularly. Most of the mutations are "private," running only in families and not outside a specific group. When the mutations exist within the family, many members will have it, the reason why so few common mutations exist.

The American College of Obstetrics and Gynecology (ACOG), American College of Medical Geneticists (ACMG) and National Institutes of Health (NIH) last year recommended that all individuals considering conception be screened for the presence of a mutated CF gene. The group examined all known mutations and identified those most prevalent for each ethnic group, and have recommended screening for the 25 which are most likely to occur (the "ACOG 25"). Each of the 25 mutations has also been ranked according to a disease severity index. For example, the severity of R117H, a rare ACOG 25 CF mutation, is associated with the presence of 5T, a variation on another region of the CF gene. Test results often show this 5T variation alone. Such results may be misleading for physicians and patients because this particular variant is not indicative of CF unless associated with the rare mutation (R117H) detected in the ACOG panel. Therefore, a reflex panel has been recommended to test for this particular variation only in the presence of the mutation.

The ACOG guidelines require that the female’s genotype be evaluated first. In the event her DNA reveals she has a CF mutation, a genetic counselor will explain the severity of CF any offspring would have, should an identical mutation be found in the male. When both parties have the same mutation, the odds are one-in-four that the offspring will be CF-positive.

Genetic Testing for Cystic Fibrosis

To discuss the current state of CF testing technology is Cindy WalkerPeach, Ph.D, of Ambion Diagnostics, a division of Ambion, Inc. in Austin, TX. Dr. WalkerPeach will make her presentation entitled, "Cystic Fibrosis Testing: Current Platforms and Emerging Technologies," during the 55th Annual Meeting of the American Association for Clinical Chemistry (AACC) in Philadelphia, PA, July 20-24, 2003.

The demand for testing has risen in the past year in response to the ACOG recommendations. Several manufacturers have developed screening tests to meet the increasing needs. Others are working on a newer generation of tests, classified as emerging technologies. Large laboratories have also conducted their own research and created in-house tests.

A New 15 Second Test

Ambion Diagnostics has developed a bead-array test that will become available in first quarter, 2004. The DNA test panel evaluates 31 CF mutations, including the 25 recommended for carrier screening by ACOG and ACMG. The test is divided into 2 parts, one for the ACOG 25 and if required, a separate reflex panel is performed to confirm the severity of detected mutation(s).

The bead-array test requires only that genomic DNA be taken from the patient, usually through a blood draw. Following the blood draw, the genomic DNA is isolated and single-tube PCR amplification of the genomic DNA is performed against the 31 different mutations. In one single reaction, the PCR products are hybridized to probes tethered onto small color-coded microspheres. Each microsphere is run through a laser beam that identifies the presence of a mutation. After hybridization, all ACOG 25 mutations are screened in 15 seconds.

A benefit of this test is allowing laboratories to run thousands of tests each week. With the dramatic increase in the desire for testing, following the ACOG recommendations, labs are experiencing delays in conducting their current tests and sending results to physicians. Another benefit of this test is that it can be easily expanded to test for selected CF mutations not included in the ACOG 25.

Conclusions

By knowing the family-specific mutations, other family members could be tested to identify CF carriers. However, since so many rare mutations have been described, not all mutations will be detected by the screening test. If the history or specific mutation is not known, a negative screening test will reduce, but not eliminate, the risk of being a carrier. The new test will allow potential parents to know more quickly if they are carriers of any of the ACOG 25 CF mutations. The hope is that for parents-to-be, such knowledge will not only help them to make more informed decisions, but also allow for treatment options that can greatly impact quality of life.

Donna Krupa | EurekAlert!
Further information:
http://www.aacc.org

More articles from Health and Medicine:

nachricht Researchers release the brakes on the immune system
18.10.2017 | Rheinische Friedrich-Wilhelms-Universität Bonn

nachricht Norovirus evades immune system by hiding out in rare gut cells
12.10.2017 | University of Pennsylvania School of Medicine

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Neutron star merger directly observed for the first time

University of Maryland researchers contribute to historic detection of gravitational waves and light created by event

On August 17, 2017, at 12:41:04 UTC, scientists made the first direct observation of a merger between two neutron stars--the dense, collapsed cores that remain...

Im Focus: Breaking: the first light from two neutron stars merging

Seven new papers describe the first-ever detection of light from a gravitational wave source. The event, caused by two neutron stars colliding and merging together, was dubbed GW170817 because it sent ripples through space-time that reached Earth on 2017 August 17. Around the world, hundreds of excited astronomers mobilized quickly and were able to observe the event using numerous telescopes, providing a wealth of new data.

Previous detections of gravitational waves have all involved the merger of two black holes, a feat that won the 2017 Nobel Prize in Physics earlier this month....

Im Focus: Smart sensors for efficient processes

Material defects in end products can quickly result in failures in many areas of industry, and have a massive impact on the safe use of their products. This is why, in the field of quality assurance, intelligent, nondestructive sensor systems play a key role. They allow testing components and parts in a rapid and cost-efficient manner without destroying the actual product or changing its surface. Experts from the Fraunhofer IZFP in Saarbrücken will be presenting two exhibits at the Blechexpo in Stuttgart from 7–10 November 2017 that allow fast, reliable, and automated characterization of materials and detection of defects (Hall 5, Booth 5306).

When quality testing uses time-consuming destructive test methods, it can result in enormous costs due to damaging or destroying the products. And given that...

Im Focus: Cold molecules on collision course

Using a new cooling technique MPQ scientists succeed at observing collisions in a dense beam of cold and slow dipolar molecules.

How do chemical reactions proceed at extremely low temperatures? The answer requires the investigation of molecular samples that are cold, dense, and slow at...

Im Focus: Shrinking the proton again!

Scientists from the Max Planck Institute of Quantum Optics, using high precision laser spectroscopy of atomic hydrogen, confirm the surprisingly small value of the proton radius determined from muonic hydrogen.

It was one of the breakthroughs of the year 2010: Laser spectroscopy of muonic hydrogen resulted in a value for the proton charge radius that was significantly...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

ASEAN Member States discuss the future role of renewable energy

17.10.2017 | Event News

World Health Summit 2017: International experts set the course for the future of Global Health

10.10.2017 | Event News

Climate Engineering Conference 2017 Opens in Berlin

10.10.2017 | Event News

 
Latest News

Electrode materials from the microwave oven

19.10.2017 | Materials Sciences

New material for digital memories of the future

19.10.2017 | Materials Sciences

Physics boosts artificial intelligence methods

19.10.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>