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 New risk factors for anxiety disorders
24.02.2017 | Julius-Maximilians-Universität Würzburg

nachricht Stingless bees have their nests protected by soldiers
24.02.2017 | Johannes Gutenberg-Universität Mainz

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Breakthrough with a chain of gold atoms

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

Im Focus: DNA repair: a new letter in the cell alphabet

Results reveal how discoveries may be hidden in scientific “blind spots”

Cells need to repair damaged DNA in our genes to prevent the development of cancer and other diseases. Our cells therefore activate and send “repair-proteins”...

Im Focus: Dresdner scientists print tomorrow’s world

The Fraunhofer IWS Dresden and Technische Universität Dresden inaugurated their jointly operated Center for Additive Manufacturing Dresden (AMCD) with a festive ceremony on February 7, 2017. Scientists from various disciplines perform research on materials, additive manufacturing processes and innovative technologies, which build up components in a layer by layer process. This technology opens up new horizons for component design and combinations of functions. For example during fabrication, electrical conductors and sensors are already able to be additively manufactured into components. They provide information about stress conditions of a product during operation.

The 3D-printing technology, or additive manufacturing as it is often called, has long made the step out of scientific research laboratories into industrial...

Im Focus: Mimicking nature's cellular architectures via 3-D printing

Research offers new level of control over the structure of 3-D printed materials

Nature does amazing things with limited design materials. Grass, for example, can support its own weight, resist strong wind loads, and recover after being...

Im Focus: Three Magnetic States for Each Hole

Nanometer-scale magnetic perforated grids could create new possibilities for computing. Together with international colleagues, scientists from the Helmholtz Zentrum Dresden-Rossendorf (HZDR) have shown how a cobalt grid can be reliably programmed at room temperature. In addition they discovered that for every hole ("antidot") three magnetic states can be configured. The results have been published in the journal "Scientific Reports".

Physicist Dr. Rantej Bali from the HZDR, together with scientists from Singapore and Australia, designed a special grid structure in a thin layer of cobalt in...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Booth and panel discussion – The Lindau Nobel Laureate Meetings at the AAAS 2017 Annual Meeting

13.02.2017 | Event News

Complex Loading versus Hidden Reserves

10.02.2017 | Event News

International Conference on Crystal Growth in Freiburg

09.02.2017 | Event News

 
Latest News

Stingless bees have their nests protected by soldiers

24.02.2017 | Life Sciences

New risk factors for anxiety disorders

24.02.2017 | Life Sciences

MWC 2017: 5G Capital Berlin

24.02.2017 | Trade Fair News

VideoLinks
B2B-VideoLinks
More VideoLinks >>>