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 Oestrogen regulates pathological changes of bones via bone lining cells
28.07.2017 | Veterinärmedizinische Universität Wien

nachricht Programming cells with computer-like logic
27.07.2017 | Wyss Institute for Biologically Inspired Engineering at Harvard

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Abrupt motion sharpens x-ray pulses

Spectrally narrow x-ray pulses may be “sharpened” by purely mechanical means. This sounds surprisingly, but a team of theoretical and experimental physicists developed and realized such a method. It is based on fast motions, precisely synchronized with the pulses, of a target interacting with the x-ray light. Thereby, photons are redistributed within the x-ray pulse to the desired spectral region.

A team of theoretical physicists from the MPI for Nuclear Physics (MPIK) in Heidelberg has developed a novel method to intensify the spectrally broad x-ray...

Im Focus: Physicists Design Ultrafocused Pulses

Physicists working with researcher Oriol Romero-Isart devised a new simple scheme to theoretically generate arbitrarily short and focused electromagnetic fields. This new tool could be used for precise sensing and in microscopy.

Microwaves, heat radiation, light and X-radiation are examples for electromagnetic waves. Many applications require to focus the electromagnetic fields to...

Im Focus: Carbon Nanotubes Turn Electrical Current into Light-emitting Quasi-particles

Strong light-matter coupling in these semiconducting tubes may hold the key to electrically pumped lasers

Light-matter quasi-particles can be generated electrically in semiconducting carbon nanotubes. Material scientists and physicists from Heidelberg University...

Im Focus: Flexible proximity sensor creates smart surfaces

Fraunhofer IPA has developed a proximity sensor made from silicone and carbon nanotubes (CNT) which detects objects and determines their position. The materials and printing process used mean that the sensor is extremely flexible, economical and can be used for large surfaces. Industry and research partners can use and further develop this innovation straight away.

At first glance, the proximity sensor appears to be nothing special: a thin, elastic layer of silicone onto which black square surfaces are printed, but these...

Im Focus: 3-D scanning with water

3-D shape acquisition using water displacement as the shape sensor for the reconstruction of complex objects

A global team of computer scientists and engineers have developed an innovative technique that more completely reconstructs challenging 3D objects. An ancient...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Clash of Realities 2017: Registration now open. International Conference at TH Köln

26.07.2017 | Event News

Closing the Sustainability Circle: Protection of Food with Biobased Materials

21.07.2017 | Event News

»We are bringing Additive Manufacturing to SMEs«

19.07.2017 | Event News

 
Latest News

New 3-D imaging reveals how human cell nucleus organizes DNA and chromatin of its genome

28.07.2017 | Health and Medicine

Heavy metals in water meet their match

28.07.2017 | Power and Electrical Engineering

Oestrogen regulates pathological changes of bones via bone lining cells

28.07.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>