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One day in 1997, Laura Gould, who was a physical therapist at the time, put her 15-month-old daughter Maria on the bed, hoping she would get a good night's sleep. Maria had a high fever the night before, but the next day she seemed to have recovered. What Ms. Gould couldn't have imagined was that Maria never woke up from her sleep. Without any warning, Maria died suddenly in her sleep. Subsequent autopsies and pathological examinations also did not reach any definitive conclusions, and maria's cause of death became a mystery.
In fact, there are not a few cases like Maria's. In the United States alone, about 400 children aged 1 to 18 (mostly between the ages of 1 and 4) die suddenly of unknown cause each year, and they die mostly in a state of sleep. Unable to identify the cause, these cases are collectively referred to as sudden unexplained death in childhood (SUDC).
It is worth mentioning that when this occurs in infants under one year of age, this symptom is called sudden infant death syndrome (SIDS). While there are similar symptoms, the degree of study of the two varies widely: Exome sequencing studies of SIDS have revealed rare mutations that cause disease; in contrast, much less attention has been paid to SUDCs, which have previously been limited to known fatal mutations. As a result, parents who have lost their children never wait for the answers they want.
Until recently, a study published in the Proceedings of the National Academy of Sciences (PNAS) finally found a breakthrough. Through all-exome sequencing, Professor Qian Yongyou's team at New York University School of Medicine revealed the true cause of death in some OFC cases: a series of genetic mutations related to epilepsy, heart rate disorders, and neurodevelopmental disorders, which caused this scene of tragedy.
In this study, Professor Qian Yongyou's team sequenced all exomes of 124 households. The families' children died suddenly of unknown cause between the ages of 11 months and 19 (mostly 1 to 4 years old), and the team sequenced the deceased and their parents.
Before the study was conducted, one phenomenon caught the attention of the research team: children who died of SUDC were 10 times more likely to develop overheated seizures than the average child. They suspect that the cause of death may be related to epilepsy and cardiac insufficiency. To that end, the team focused on 137 genes associated with these diseases.
Sequencing results showed that 11 of the 124 deceased (about 9 percent) had mutations in genes that regulate calcium ion function in brains and cardiomyocytes. Calcium ion signaling is important for the function of neurons and cardiomyocytes. When the correct signal is received, the cell opens an ion channel, allowing calcium ions to cross the cell membrane and form an electric current. When the calcium ion signal is abnormal, it can lead to arrhythmias or epilepsy, both of which can have fatal consequences.
Comparison of the mutations observed in the study with the expected (Image source: References[1])
Notably, most of the mutations revealed in this study are entirely new. Sequencing results for the parents of these children showed that the mutations were not genetic products, but appeared randomly in newborns.
"Our study is the largest of its kind, and it confirms for the first time that there are genetic factors in the emergence of SUDCs," said Professor Qian Yongyou, "New research on gene mutations will gradually uncover the pathogenic mechanism and lay the foundation for future new therapies." ”
Not long ago, another study published in Genes in Medicine also included sequencing studies of SUDCs: Of the 32 children who died from SUDC, 6 developed associated mutations. Notably, both studies found that mutations in the SCN1A gene, which is associated with epilepsy, are associated with sudden death in children.
This study reveals the pathogenic genes of some SUDC cases, of course, we also see that there are still 90% of the causes that are not yet clear, and more follow-up research is obviously needed. At this point, the story about the paper itself is nearing its end. But behind this paper, there is another character that should not be overlooked.
In this PNAS paper, the second author is none other than Ms. Gould, who lost her child 25 years ago. After seeing her child die inexplicably in front of her, a sad Ms. Gould realized that the scientific community knew almost nothing about SUDC, and the first problem with conducting related research was the lack of funding.
Ms. Laura Gould's efforts have fueled research on SUDC (Image: SUDC Foundation)
To give herself and other parents who have lost their children an answer, and to avoid such tragedies in the future, Ms. Gould joined forces with others to create the SUDC Foundation. It was this nonprofit foundation that funded the research to support parents who had lost their children. Ms. Gould, who is currently a scientist at New York University School of Medicine, is personally involved in research to find the answer she's been looking forward to for 25 years.
This development is a good start for Ms. Gourd, but the truth about the large number of SUDC cases remains elusive. However, in her view, this progress also paves the way for future work.
"The sudden death of a child can bring endless grief and confusion [to the parents]," Ms. Gould said, "and even comfort is isolated for such a rare tragedy." And these people together, it will be of great help. Therefore, I encourage those who have suffered the same pain to join this organization and inform the research. ”
Cover image source: 123RF
References (can be viewed by swiping up and down)
[1] Matthew Halvorsen et al, De novo mutations in childhood cases of sudden unexplained death that disrupt intracellular Ca2+ regulation. PNAS (2022). https://doi.org/10.1073/pnas.2115140118
[2] Geneticists find clues to sudden unexplained child deaths. Retrieved Feb 10th, 2022 from https://www.science.org/content/article/geneticists-find-clues-sudden-unexplained-child-deaths
[3] First genetic risk factors identified for sudden unexplained death in children after age one. Retrieved Dec 22nd, 2021 from https://www.sciencedaily.com/releases/2021/12/211220190653.htm
[4] Mother Aims to Find Cause, Aid Others Mourning Sudden Child Death. Retrieved Jan 26th, 2022 from https://www.webmd.com/parenting/news/20220126/mother-aims-find-cause-aid-others-sudden-child-death
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