Kethleen’s drama and the genetic causes behind the deaths of her four children
[ad_1]
“The saddest thing about life right now is that science gathers knowledge faster than society gathers wisdom.” This is what the great writer and scientist said some time ago Isaac Asimov (1920-1992). I thought about this statement after I was released from prison Kethleen Folbigg, sentenced to 40 years in prison on charges of carrying her four children to their deaths. On 5 June, after having spent the last twenty years in prison, Folbigg was released from prison with a ruling by the Australian Court of Justice which held that there was “reasonable doubt as to Mrs Folbigg’s guilt for each of the crimes for which she was was originally processed”. A reversal that has created quite a stir given the horrible crimes of which the woman was accused.
Newborn screening project: one in 10 has genetic mutations
Deaths from genetic causes
But what new evidence led to Folbigg’s release? In the process, only the complete analysis of Folbigg’s DNA and that of her 4 four children – DNA obtained from biological samples derived at the time from the autopsy and suitably preserved – made it possible to demonstrate that Mrs. Folbigg’s children are deceased for genetic causes. The two daughters inherited from their mother a rare mutation in the calmodulin gene, one of the known causes of sudden death to date. Calmodulin controls the calcium concentration in the cells and regulates the contractions of the heart. In sudden death, defined as a natural event that occurs suddenly, death is instantaneous and occurs within one hour of the onset of acute symptoms. For it to fall into this category, the fatal event must have the characteristics of unpredictability, i.e. occur in subjects in an apparent state of good health. This is the case, for example, of athletes, even in the absence of obvious cardiac dysfunction.
Crib death syndrome
The mutations of the genes of sudden death are also found in SIDS, or in the “cot death syndrome”. It is estimated that in Italy the prevalence of SIDS is in the order of 0.5-1.5‰ of live births, with a peak between 2 and 4 months of age. SIDS is due to various causes that involve a complex interaction of individual genetic susceptibility with environmental factors or problems related to anomalies during development (prematurity for example). In recent years, several responsible genes have been identified when mutated, including the CALM2 gene found in Folbigg and her two daughters. Forensic researchers have not only identified the pathogenic mutation, but also demonstrated that the G114R mutation produces a malfunctioning calmodulin that causes a rare heart disease (calmodulinopathy), which causes some forms of SIDS.
So one wonders: why is the mother not sick despite having the mutation that she passed on to her daughters? An element that does not surprise geneticists: it is known that these mutations often have incomplete penetrance, i.e. they do not manifest themselves in some individuals due to phenomena of genetic resilience, which we are only able to partially understand today.
Sudden death, “out of control” kick could become a target for treatment
by Federico Mereta
The two sons
And the two sons? The analysis of the DNA on them, who also died soon after birth, although with a slightly different clinical picture from their little sisters, revealed two rare mutations in another gene called Bsn. This gene has only recently been associated with causes of lethal neonatal epilepsies in a mouse model genetically engineered to study its biological effects. In addition, also recently, families with Bsn mutations that cause epileptic forms even at an early age have been described.
However, the Bsn mutations, to produce disease, must act in pairs (recessive): in short, for ‘true’ epilepsy a patient must have two Bsn mutations in his DNA. The picture, therefore, in the light of the new scientific investigations, has become clearer: the two males had two Bsn mutations (one received from the mother, which has been ascertained, and one from the father who did not consent to the verification by not donating the his DNA). Thus, four children born doomed to death for inheriting mutations in two different genes. How likely is such a chilling coincidence to occur?
A chilling coincidence
This calculation is simple for forensic geneticists, and turns out to be 1/64. Low, certainly, but possible. Solving this case required the expertise of 30 different investigators, including my colleague and friend Peter Schwartz dell’Auxologico of Milan, an expert recognized worldwide for the genetics of sudden death and other colleagues from different countries who testified as independent experts.
Following the woman’s release, the scientist-experts who produced the results of not guilty in the new trial have asked for a legal reform that allows the acquisition of emerging scientific evidence for possible revisions of a trial even after years. Scientific knowledge is evolving rapidly, especially in forensic genetics, thanks to new DNA analysis techniques and functional assessments of the role of genetic variants identified in genome analysis. This experience demonstrates how science and justice systems can and should work together also in order to create a “legal system more sensitive to science”. One possibility could be the regulation of appointments of highly qualified and highly specialized experts.
Artificial intelligence for new therapies or for screening 2.0, the doctor of the future is already here
by Elisa Manacorda
Cases to be reviewed
The news tells us that there are many cases that could be re-examined in the light of new scientific knowledge or with the presentation of new evidence to be examined. However, it is evident that not even science, despite the giant progress it has accustomed us to over time, can alone provide all the answers. Sometimes, boundaries and interpretations are blurred, requiring constant caution and verification. With the application of scientific knowledge in the forensic field, the role of the scientist in society has profoundly changed.
Scientists are required, with a great sense of balance and responsibility, to be present, to explain, to offer solutions, to be both advisers and compasses, both for private citizens and for government and judicial bodies. A delicate task that must never get out of hand: the purpose of science, in addition to acquiring new knowledge, remains that of knowing how to use it for everyone’s benefit.
Giuseppe Novelli is a geneticist at the Tor Vergata University in Rome
[ad_2]
Source link
