Navigation Links
Genetic research unveils common origins for distinct clinical diagnoses
Date:3/9/2008

Researchers at Johns Hopkins have discovered that two clinically different inherited syndromes are in fact variations of the same disorder. Reporting in the April issue of Nature Genetics, the team suggests that at least for this class of disorders, the total number and strength of genetic alterations an individual carries throughout the genome can generate a range of symptoms wide enough to appear like different conditions.

Were finally beginning to blur the boundaries encompassing some of these diseases by showing that they share the same molecular underpinnings, says Nicholas Katsanis, Ph.D., an associate professor of ophthalmology at the McKusick-Nathans Institute of Genetic Medicine at Hopkins. This is important progress for several reasons. First, knowing whats going on molecularly and being able to integrate rarer conditions under common mechanisms allows us to potentially help more people at once. Second, clinicians can finally begin to offer more accurate diagnoses based on what really matters: the state of affairs at the cellular/biochemical level. In time, this will empower genetic counseling and much improved patient management.

Katsaniss team studies Bardet-Biedl syndrome (BBS), a rare so-called ciliopathy that is characterized by a combination of vision loss, obesity, diabetes, extra digits and mental defects and caused by faulty cilia, tiny hairlike projections found on almost every cell of the body. Recently they started looking at another disease, Meckel-Gruber syndrome (MKS), which also shows cilia dysfunction but is clinically distinct from BBS and generally associated with prenatal or newborn death.

While these two groups of patients exhibit such different clinical outcomes, the genes associated with both syndromes all seemed to be pointing at the same culprit: cilia, says Katsanis. So we wondered if BBS and MKS might actually represent different flavors of the same disease.

The researchers sequenced the MKS genes from 200 BBS patients and found six families that, in addition to carrying BBS genetic mutations, also carried mutations in MKS genes. To figure out what, if any, effect these MKS mutations have on BBS, the team used a system they previously developed in zebrafish.

Knocking out BBS genes in zebrafish generates short fish with even shorter tails, among other malformations. Injecting normal BBS genes into these fish rescues them, resulting in normal looking fish.

The researchers reasoned that if MKS and BBS are indeed the same condition, then fish with the MKS genes knocked out should mimic the BBS knockout fish. They did. The team then went on to test mutant versions of MKS genes in BBS fish and found that three genes originally attributed to MKS do indeed cause BBS or render the BBS defects more pronounced, increasing the number of BBS genes to 14 in total.

From a clinical perspective, these two syndromes look nothing alike, but molecularly, the genes involved clearly participate in the same fundamental processes, says Katsanis. This means that Meckel-Gruber and Bardet-Biedel actually represent a continuum of one disease. This never would have been discovered in the clinic-only molecular analysis can reveal these things.

But what does this mean for clinicians and the diagnosis and treatment of these syndromes" Katsanis hopes that the growing body of molecular data will help move medicine away from symptom-defined syndromes, which can leave clinicians struggling with ambiguous diagnoses, to approaching disorders from a molecular standpoint. We now have the possibility of merging several rare disorders, he says. And their gross sum now turns out to be fairly common; hopefully this will now put them on the radar for drug development and other therapies.


'/>"/>

Contact: Audrey Huang
audrey@jhmi.edu
410-614-5105
Johns Hopkins Medical Institutions
Source:Eurekalert

Related medicine news :

1. New stem cell technique improves genetic alteration
2. Einstein researchers genetically engineer immune cells into potent weapons for battling HIV
3. Genetic Test Predicts Response to Warfarin
4. New revelations in epigenetic control shed light on breast cancer
5. Researchers identify new genetic marker for breast cancer
6. Anti-Aging/Genetic Health Leader Suracell, Inc. Expands Internationally
7. Adult stem cell changes underlie rare genetic disease associated with accelerated aging
8. Genetic Factors for Smoking Boost Chronic Bronchitis Risk
9. Genetic factors in smoking also increase risk of chronic bronchitis
10. Dr. Robert Leonard First in New England to Offer Genetic Test for Male Pattern Baldness
11. U of Minn researchers discover genetic cancer link between humans and dogs
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:10/13/2017)... ... October 13, 2017 , ... ... Arkansas that offers insurance and financial preparation services, is providing an update on ... Rescue organization. , Rock City Rescue is a locally recognized nonprofit that provides ...
(Date:10/13/2017)... ... October 13, 2017 , ... The International Association ... standards of excellence for the field of eating disorders, announces the opening of ... 2018 in Orlando, Florida at the Omni Resort at ChampionsGate. , ...
(Date:10/13/2017)... ... ... Apple Rehab Shelton Lakes , which specializes in the delivery of sub-acute ... of a disaster drill on October 3rd. , Apple Rehab participated with the Shelton ... well as the Connecticut Long Term Care Mutual Aid Plan (LTC-MAP). The LTC-MAP ...
(Date:10/13/2017)... ... ... Global Healthcare Management’s 4th Annual Kids Fun Run brought out many kids ... sponsored by Global Healthcare Management’s CEO, Jon Letko, is aimed at getting kids excited ... all ages; it is a non-competitive, non-timed event, which is all about having fun ...
(Date:10/13/2017)... ... ... “The Journey: From the Mountains to the Mission Field”: the story of a ... “The Journey: From the Mountains to the Mission Field” is the creation of published ... all ages and currently teaches a class of ladies at her church, which she ...
Breaking Medicine News(10 mins):
(Date:9/19/2017)... Mich. , Sept. 19, 2017 HistoSonics, Inc., a venture-backed medical device company ... destruction of targeted tissues, announced three leadership team developments today:   ... PhD ... ... Veteran medical device executive Josh ...
(Date:9/18/2017)... 2017 EpiVax, Inc. ("EpiVax") a ... immune engineering, today announced a new NIH-funded ... ... and presents a challenge for traditional flu ... be effective. Using state-of-the-art bioinformatics and molecular modeling methods, ...
(Date:9/12/2017)... -- Consumer reviews on the independent review site Consumer Affairs ... for hearing aids, ranking it higher than Miracle Ear ™, ... ... Hearing Aids ... store that provides high performance, state-of-the-art, German-engineered hearing aids directly to ...
Breaking Medicine Technology: