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


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:

More articles from Life Sciences:

nachricht Gene therapy shows promise for treating Niemann-Pick disease type C1
27.10.2016 | NIH/National Human Genome Research Institute

nachricht 'Neighbor maps' reveal the genome's 3-D shape
27.10.2016 | International School of Advanced Studies (SISSA)

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Etching Microstructures with Lasers

Ultrafast lasers have introduced new possibilities in engraving ultrafine structures, and scientists are now also investigating how to use them to etch microstructures into thin glass. There are possible applications in analytics (lab on a chip) and especially in electronics and the consumer sector, where great interest has been shown.

This new method was born of a surprising phenomenon: irradiating glass in a particular way with an ultrafast laser has the effect of making the glass up to a...

Im Focus: Light-driven atomic rotations excite magnetic waves

Terahertz excitation of selected crystal vibrations leads to an effective magnetic field that drives coherent spin motion

Controlling functional properties by light is one of the grand goals in modern condensed matter physics and materials science. A new study now demonstrates how...

Im Focus: New 3-D wiring technique brings scalable quantum computers closer to reality

Researchers from the Institute for Quantum Computing (IQC) at the University of Waterloo led the development of a new extensible wiring technique capable of controlling superconducting quantum bits, representing a significant step towards to the realization of a scalable quantum computer.

"The quantum socket is a wiring method that uses three-dimensional wires based on spring-loaded pins to address individual qubits," said Jeremy Béjanin, a PhD...

Im Focus: Scientists develop a semiconductor nanocomposite material that moves in response to light

In a paper in Scientific Reports, a research team at Worcester Polytechnic Institute describes a novel light-activated phenomenon that could become the basis for applications as diverse as microscopic robotic grippers and more efficient solar cells.

A research team at Worcester Polytechnic Institute (WPI) has developed a revolutionary, light-activated semiconductor nanocomposite material that can be used...

Im Focus: Diamonds aren't forever: Sandia, Harvard team create first quantum computer bridge

By forcefully embedding two silicon atoms in a diamond matrix, Sandia researchers have demonstrated for the first time on a single chip all the components needed to create a quantum bridge to link quantum computers together.

"People have already built small quantum computers," says Sandia researcher Ryan Camacho. "Maybe the first useful one won't be a single giant quantum computer...

All Focus news of the innovation-report >>>



Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

Agricultural Trade Developments and Potentials in Central Asia and the South Caucasus

14.10.2016 | Event News

World Health Summit – Day Three: A Call to Action

12.10.2016 | Event News

Latest News

How nanoscience will improve our health and lives in the coming years

27.10.2016 | Materials Sciences

OU-led team discovers rare, newborn tri-star system using ALMA

27.10.2016 | Physics and Astronomy

'Neighbor maps' reveal the genome's 3-D shape

27.10.2016 | Life Sciences

More VideoLinks >>>