丁香园AV

LEFT-RIGHT: ERIN LIN, GLEN TIBBITS, SANAM SHAFAATTALAB, ALISON LI

Certain cases of sudden unexpected death in infants are linked with genetic variants that cause cardiac arrest

A team of researchers from Canada and the US has found that a newly identified genetic variant can cause sudden cardiac arrest (SCA) which may explain certain cases of sudden unexpected death in infants (SUDI).

The research was conducted at 丁香园AV under the supervision of biomedical physiology and kinesiology professor Glen Tibbits, who is also an investigator at BC Children鈥檚 Hospital.

鈥淪UDI is a devastating occurrence for parents and health care practitioners particularly when post-mortem analysis is unable to pinpoint the cause of death鈥� Tibbits says.

鈥淭hanks to post-mortem molecular genetic testing and innovative new technologies using induced pluripotent stem cells and genome editing, a significant number of SUDI cases can be attributed to SCA鈥� he adds.

The work stemmed from Sanam Shafaattalab鈥檚 PhD research and included contributions from fellow 丁香园AV researchers Alison Li, Eric Lin, Laura Dewar and Charlie Stevens.  The team also received assistance from researchers at BC Children鈥檚 Hospital Research Institute, UBC, the University of Calgary and Ohio State University to develop the experimental platform used to assess genetic variants that could potentially be causal in sudden cardiac death of infants. (SCDI).

Using this platform, the team was able to introduce the TNNI1 R37C^+/- variant into human induced pluripotent stem cells (hiPSCs) and differentiate them into beating heart cells in the lab. Monitoring heart beat patterns under control conditions allowed the team to detect abnormal electrical activity or arrhythmias.

Tibbits explains that in people without the genetic variant, as one鈥檚 heart rate increases with exercise or stress, the period of electrical excitation shortens to accommodate the higher rates.  However, in people with this genetic variant, the shortened period of electrical excitation does not occur. Instead, Tibbits says that the mutation disrupts neonatal cardiac physiology by altering how calcium in the heart cells is handled. 鈥淭his can then trigger-life threatening arrhythmias in newborn鈥檚 hearts鈥�, he adds.

Tibbits cautions that there is still work to be done before this discovery can be used to develop a treatment. 鈥淗owever, we will now inform the cardiologists and genetic counsellors who will work with families, parents, and siblings of the deceased infants to identify carriers of this variant and to develop a strategy to reduce SUDI within that community鈥� says Tibbits. 

The experimental platform developed by the team will also be useful in investigating other types of inherited arrhythmias induced by other genetic variants that might increase the risk for SCA.

The study was funded by the Stem Cell Network of Canada and CIHR and was published last week in the 

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