Qian Yongyou's team discovered for the first time genetic risk factors for unexplained sudden death in children

In the United States, about 400 children over 1 year old die suddenly every year
.

For the elderly, about a quarter of sudden death cases can be explained by pathogenic heart gene mutations.

Researchers from New York University's Grossman School of Medicine and other institutions have recently sequenced and analyzed the genomes of 124 parent-child trio (children died of SUDC)
.

They found multiple new mutations that focused on genes linked to the heart and epilepsy

Professor Richard Tsien of New York University’s Grossman School of Medicine said: “Our study is the largest of its kind so far.
It is the first to prove that there is a clear genetic cause for sudden death of unknown cause in children
.

In addition to providing information for the parents of patients.

In this analysis, the researchers performed whole-exome sequencing on 124 children who died suddenly and their parents.
The average age of these children at death was 34.
2 months
.

They identified 125 new mutations, including 116 single nucleotide variants (SNV) and 9 indels (indels) from sick children, and verified them by Sanger sequencing

Compared with the two control trio groups, the SUDC cohort did not carry too many non-synonymous mutations
.

However, in a group of 137 genes related to heart or epilepsy, the researchers found that SUDC patients do have a higher mutation load

They constructed a protein interaction network of SUDC-related mutations
.

Related genes can be divided into four clusters, one of which contains CACNA1C, CALM1, GNAO1, RYR2, SCN1A and TNNI3, all of which are in the CardiacEpilepsy gene set

As a result, the researchers expanded their analysis to include genes outside of the CardiacEpilepsy gene set, such as those related to neurodevelopmental disorders
.

They found that there is evidence that there is a genetic overlap between sudden child death of unknown cause and neurodevelopmental disorders (such as autism and stunting)

In total, researchers found mutations that could lead to death in 11 SUDC cases, which is close to 9%
.

The researchers pointed out that multiple mutations can affect calcium ion signaling, and this signaling is important to the heart and brain
.

For example, the CACNA1C gene in two cases has mutations, which encodes voltage-dependent L-type calcium channel pore-forming subunits

They also pointed out that most of the children in the cohort died while sleeping or resting, so their next step is to study how sleep vs.
wakefulness or rest vs.
exercise affects the risk of SUDC
.

Original Search

De novo mutations in childhood cases of sudden unexplained death that disrupt intracellular Ca2+ regulation

PNAS December 28, 2021 118 (52) e2115140118; https://doi.
org/10.
1073/pnas.
2115140118