Navigation Links
Genetic analyses reveal novel mutations as causes of startle disease
Date:8/7/2012

Two studies published in the Journal of Biological Chemistry identify genetic mutations that play important roles in the condition commonly referred to as startle disease. Startle disease is characterized by an exaggerated response to noise and touch, which can interfere with breathing, cause catastrophic falls and even result in death.

The newly identified genetic mutations affect how the signaling molecule glycine, which is responsible for sending messages between nerve cells, is both moved around and used in these cells.

Startle disease, or hyperekplexia, emerges after birth, and while the symptoms usually diminish they sometimes continue into adulthood. The abnormal startle response is caused by glitches in glycine signaling.

Glycine is a small amino acid with various roles in the cell, one of which is to transmit inhibitory signals between nerve cells. In startle disease, defective proteins prevent cells from receiving the inhibitory signals that normally control a person's response to noise and touch. The result is the amplified, harmful response.

Startle disease is caused by mutations in multiple genes that encode proteins involved in glycine signaling. For example, one well-known cause is mutation of the glycine receptor alpha1 subunit gene.

But many cases do not involve that gene or the handful of others that have been given close scrutiny, according to Robert Harvey at University College London, one of the JBC authors. Working together with Mark Rees at the Institute of Life Science, Swansea University, another prominent cause of startle disease was discovered mutations in the gene for a glycine transporter known as GlyT2.

Rees' group performed genetic analyses of 93 patients across the globe and identified 19 new recessive mutations in GlyT2. Experiments using molecular models and cell lines in Harvey's group showed that these mutations resulted either in the loss or reduction of glycine uptake by GlyT2.

"Our study represents the largest multicenter screening study for GlyT2 mutations in hyperekplexia to date," the authors wrote in their paper. They went on to say the work triples the number of known cases with these mutations, "firmly establishing mutations in the GlyT2 gene as a second major cause of startle disease."

In the other JBC paper, Beatriz Lpez-Corcuera at the Universidad Autnoma de Madrid in collaboration with Cecilio Gimnez and Pablo Lapunzinas groups at the IdiPAZ-Hospital Universitario La Paz and colleagues report another novel genetic mutation in GlyT2 as the cause of startle disease in eight patients from Spain and the United Kingdom.

Lpez-Corcuera said: "The mutation that we discovered is the first common dominant mutation in the GlyT2 gene," meaning that inheritance of a single defective copy of the gene causes disease.

The team found that the mutation hindered proper expression of the GlyT2 transporter at the cell membrane and changed how GlyT2 itself functions.

Lpez-Corcuera explains that this GlyT2 mutation reduces glycine uptake, which decreases the amount of glycine subsequently released and ultimately hinders transmission of the inhibitory signal. Lpez-Corcuera suggests that these results may explain the symptoms observed in the patients and "could be useful for future pharmacological approaches."

From the articles:

"A novel dominant hyperekplexia mutation Y705C alters trafficking and biochemical properties of the presynaptic glycine transporter GlyT2" by Cecilio Gimnez, Gonzalo Prez-Siles, Jaime Martnez- Villarreal, Esther Arribas-Gonzlez, Esperanza Jimnez, Enrique Nez, Jaime de Juan-Sanz, Enrique Fernndez-Snchez, Noem Garca-Tardn, Ignacio Ibez, Valeria Romanelli, Julin Nevado, Victoria M James, Maya Topf, Seo-Kyung Chung, Rhys H Thomas, Lourdes R Desviat, Carmen Aragn, Francisco Zafra, Mark I Rees, Pablo Lapunzina, Robert J Harvey, and Beatriz Lpez- Corcuera


'/>"/>
Contact: Angela Hopp
ahopp@asbmb.org
240-283-6614
American Society for Biochemistry and Molecular Biology
Source:Eurekalert

Related medicine news :

1. IntegraGen launches ARISk test, a genetic screening tool for autism in high-risk children
2. 2 genetic deletions in human genome linked to the development of aggressive prostate cancer
3. Head, Body Lice Are Genetically Very Similar
4. Certain Genetic Regions May Be Tied to Osteoporosis
5. Study of half siblings provides genetic clues to autism
6. Genetic variants, tobacco exposure and lung cancer risk
7. Research Gets Closer to Genetic Roots of Glaucoma
8. Moffitt researcher awarded GE grant to develop tool to detect breast cancer metastasis genetic risks
9. Genetically modified T cell therapy shown to be safe, lasting in decade-long study of HIV patients
10. Some women may be genetically predisposed to smoking-related hot flashes
11. Genetic abnormalities in benign or malignant tissues predict relapse of prostate cancer
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:10/13/2017)... ... 2017 , ... The International Association of Eating Disorders Professionals ... the field of eating disorders, announces the opening of early registration for the ... at the Omni Resort at ChampionsGate. , The annual iaedp™ Symposium ...
(Date:10/13/2017)... (PRWEB) , ... October 13, ... ... School of Pharmacy (SOP) alumni Hannah Randall, PharmD ‘17, and Jennifer Huggins, ... professionals on guideline updates for the primary prevention of cardiovascular diseases during ...
(Date:10/13/2017)... ... October 13, 2017 , ... Apple Rehab Shelton Lakes ... a mock evacuation of the facility as part of a disaster drill on October ... Hose EMS and Shelton City Emergency Manager, as well as the Connecticut Long ...
(Date:10/13/2017)... ... ... The Visiting Nurse Association (VNA) of Somerset Hills is proud to host ... items from across the nation, this holiday-themed event will raise funds and awareness for ... The boutique will be open Saturday, November 4 (10:00 a.m. – 5:00 p.m.) ...
(Date:10/13/2017)... ... ... Global Healthcare Management’s 4th Annual Kids Fun Run brought out many kids this ... by Global Healthcare Management’s CEO, Jon Letko, is aimed at getting kids excited about ... ages; it is a non-competitive, non-timed event, which is all about having fun and ...
Breaking Medicine News(10 mins):
(Date:9/28/2017)... Hill-Rom Holdings, Inc. (NYSE: HRC), will host its fiscal ... Friday, November 3, 2017, beginning at 7:00 a.m. (CDT) ... a.m. (CDT) / 9:30 a.m. (EDT). In ... guidance for 2018, Hill-Rom executives will also highlight the ... long-range financial outlook through 2020. ...
(Date:9/27/2017)... , Sept. 27, 2017  DarioHealth Corp. (NASDAQ: DRIO), a leading global ... that its MyDario product is expected to appear on The Dr. Oz ... Dr. Oz Show airs in your area: http://www.doctoroz.com/page/where-watch-dr-oz-show ... The nine-time Emmy award-winning, The Dr. Oz Show kicked ... The segment features ...
(Date:9/23/2017)... -- Janssen Biotech, Inc. (Janssen) announced today that it ... Food and Drug Administration (FDA) for the Biologics License ... of moderately to severely active rheumatoid arthritis (RA). The ... to further evaluate the safety of sirukumab in the ... "We are disappointed by ...
Breaking Medicine Technology: