Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

New Study Identifies Additional Genetic Mutations in SIDS Babies: Focus is on the Autonomic Nervous System

20.08.2004


A new study has identified mutations in genes pertinent to the autonomic nervous system among babies who died of sudden infant death syndrome (SIDS) that might explain why they died. The study appears in the September issue of Pediatric Research.



Dr. Debra E. Weese-Mayer, professor of pediatrics and director of Pediatric Respiratory Medicine at Rush University Medical Center, and colleagues at Rush and at the University of Pittsburgh conducted a case-control study in which they compared genetic material from 92 SIDS babies and 92 control subjects (who survived the first year of life and had no family history for autonomic diseases).

Her study found 11 different protein-changing rare mutations in 14 of the 92 SIDS cases but only one such mutation in two of the 92 control cases. Of the 15.2 percent of the SIDS babies who had one of these mutations, 71 percent were African American babies, an observation that may explain in part the ethnic disparity in SIDS, Weese-Mayer said.


SIDS is defined as the sudden and unexpected death of an infant under one year of age that remains unexplained after a thorough clinical history, death scene investigation and postmortem examination. Public health measures have been successful in reducing the mortality rate of babies from SIDS from 1.2 deaths per 1000 live births in 1992 to 0.55 per 1000 births in 2001. However, Weese-Mayer pointed out that black infants have a higher SIDS incidence and a slower decline rate compared with white infants.

"Tragically, infants of all ethnic groups continue to succumb to SIDS despite many parents demonstrating full compliance with known modifiable risk factors," she said.

The realization that even with the Back to Sleep campaigns, nearly 2,300 babies were still dying each year from SIDS in the U.S., many of whom had no identifiable risk factors or behavioral compliance issues, spurred researchers like Weese-Mayer to pursue non-traditional explanations for SIDS. In 2000, Boston researchers identified decreased serotonergic receptor binding in the brainstems of SIDS victims. Then in 2001, Japanese researchers studied the serotonin transporter gene promoter region and discovered an association between the long allele and SIDS in Japanese babies.

In 2003 Weese-Mayer and colleagues confirmed this association in white and African American SIDS cases relative to controls. Later in the same year, Weese-Mayer and colleagues reported an association between SIDS and a serotonin transporter gene intron 2 polymorphism, also known to regulate serotonin transporter expression. The association was significant in black SIDS cases vs. controls, with the SIDS-associated genotype leading to more effective transporter production. Further, the SIDS-related polymorphisms in the promoter and intron 2, when paired, were significantly associated with SIDS in the black subgroup. Taken together, these results provide strong evidence for a relationship between SIDS risk and serotonin transporter gene activity and represent an important step in the study of a genetic basis for SIDS.

The serotonin connection provided the logical segue to the current study by Weese-Mayer and colleagues. Specifically, serotonin influences a broad range of physiological systems and is involved in ANS regulation. Dysfunction in the ANS has been reported among infants who have succumbed to SIDS. Accordingly, to further elucidate the genetic profile that might increase an infant’s vulnerability to SIDS, Dr. Weese-Mayer and colleagues focused on genes pertinent to the embryologic origin of the ANS. This approach has been successful in clarifying the genetic basis of idiopathic congenital central hypoventilation syndrome (CCHS), also known to have associated ANS dysregulation and thought to be related to SIDS.

Children with CCHS have been recently identified as heterozygous for the polyalanine expansion mutation in the PHOX2b gene in up to 97% of cases. Just as in the early investigation of CCHS, Dr. Weese-Mayer and colleagues hypothesized that a subset of SIDS cases might have unique mutations or polymorphisms in genes identified embryologically or through knock-out models to be involved in ANS regulation. The specific genes reported in this new publication include MASH1, BMP2, PHOX2a, PHOX2b, RET, ECE1, EDN1, TLX3 and EN1.

"These data represent further refinement of the genetic profile that might place an infant at increased risk for SIDS," Weese-Mayer concluded.

These results represent the first report describing analysis of homeobox and signal transduction genes important in specifying cell fate in ANS differentiation in SIDS cases. The observation that none of the SIDS cases demonstrated the PHOX2b mutation previously identified in CCHS indicates less specific overlap between the two diseases than previously considered (children with CCHS have generalized ANS dysregulation and typically present in the newborn period requiring artificial ventilatory support; infants who succumb to SIDS are seemingly normal yet have ANS dysregulation). However, as families of CCHS probands?? have a higher incidence of SIDS history in a family member, it may still be appropriate to evaluate SIDS cases for the PHOX2b mutation to ascertain that CCHS was not the cause of death.

The mutations identified in this study may be benign polymorphisms or may be mutations specifically related to the SIDS phenotype. The greatest number of rare mutations was identified in the RET gene. This is of particular interest because of the relationship of RET to Hirschsprung disease and to CCHS, and because of the RET knockout model with a depressed ventilatory response to inhaled carbon dioxide with decreased frequency and tidal volume. The knock out models for ECE1 and TLX3 also include impaired breathing and/or early death in the mouse phenotype, with suggestion of a central respiratory deficit. Further research is necessary to better understand the role of these and other genes in the SIDS phenotype and in explaining the ethnic disparity in SIDS. Once the genetic profile is complete, then intervention strategies can be considered and ideally implemented.

Chris Martin | EurekAlert!
Further information:
http://www.rush.edu

More articles from Life Sciences:

nachricht Cancer diagnosis: no more needles?
25.05.2018 | Christian-Albrechts-Universität zu Kiel

nachricht Less is more? Gene switch for healthy aging found
25.05.2018 | Leibniz-Institut für Alternsforschung - Fritz-Lipmann-Institut e.V. (FLI)

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Powerful IT security for the car of the future – research alliance develops new approaches

The more electronics steer, accelerate and brake cars, the more important it is to protect them against cyber-attacks. That is why 15 partners from industry and academia will work together over the next three years on new approaches to IT security in self-driving cars. The joint project goes by the name Security For Connected, Autonomous Cars (SecForCARs) and has funding of €7.2 million from the German Federal Ministry of Education and Research. Infineon is leading the project.

Vehicles already offer diverse communication interfaces and more and more automated functions, such as distance and lane-keeping assist systems. At the same...

Im Focus: Molecular switch will facilitate the development of pioneering electro-optical devices

A research team led by physicists at the Technical University of Munich (TUM) has developed molecular nanoswitches that can be toggled between two structurally different states using an applied voltage. They can serve as the basis for a pioneering class of devices that could replace silicon-based components with organic molecules.

The development of new electronic technologies drives the incessant reduction of functional component sizes. In the context of an international collaborative...

Im Focus: LZH showcases laser material processing of tomorrow at the LASYS 2018

At the LASYS 2018, from June 5th to 7th, the Laser Zentrum Hannover e.V. (LZH) will be showcasing processes for the laser material processing of tomorrow in hall 4 at stand 4E75. With blown bomb shells the LZH will present first results of a research project on civil security.

At this year's LASYS, the LZH will exhibit light-based processes such as cutting, welding, ablation and structuring as well as additive manufacturing for...

Im Focus: Self-illuminating pixels for a new display generation

There are videos on the internet that can make one marvel at technology. For example, a smartphone is casually bent around the arm or a thin-film display is rolled in all directions and with almost every diameter. From the user's point of view, this looks fantastic. From a professional point of view, however, the question arises: Is that already possible?

At Display Week 2018, scientists from the Fraunhofer Institute for Applied Polymer Research IAP will be demonstrating today’s technological possibilities and...

Im Focus: Explanation for puzzling quantum oscillations has been found

So-called quantum many-body scars allow quantum systems to stay out of equilibrium much longer, explaining experiment | Study published in Nature Physics

Recently, researchers from Harvard and MIT succeeded in trapping a record 53 atoms and individually controlling their quantum state, realizing what is called a...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

12th COMPAMED Spring Convention: Innovative manufacturing processes of modern implants

28.05.2018 | Event News

In focus: Climate adapted plants

25.05.2018 | Event News

Save the date: Forum European Neuroscience – 07-11 July 2018 in Berlin, Germany

02.05.2018 | Event News

 
Latest News

International Workshop Sees Central Role for Solar in Transforming the World Energy Economy

28.05.2018 | Seminars Workshops

Cognitive Power Electronics 4.0 is gaining momentum

28.05.2018 | Trade Fair News

Organic light-emitting diodes become brighter and more durable

28.05.2018 | Physics and Astronomy

VideoLinks
Science & Research
Overview of more VideoLinks >>>