Monday, March 8, 2021

Infanticide vs. inherited cardiac arrhythmias

Brohus M, Arsov T, Wallace DA, Jensen HH, Nyegaard M, Crotti L, Adamski M, Zhang Y, Field MA, Athanasopoulos V, Baró I, Ribeiro de Oliveira-Mendes BB, Redon R, Charpentier F, Raju H, DiSilvestre D, Wei J, Wang R, Rafehi H, Kaspi A, Bahlo M, Dick IE, Chen SRW, Cook MC, Vinuesa CG, Overgaard MT, Schwartz PJ. Infanticide vs. inherited cardiac arrhythmias. Europace. 2020 Nov 17:euaa272. doi: 10.1093/europace/euaa272. Epub ahead of print. PMID: 33200177.

Abstract

Aims: In 2003, an Australian woman was convicted by a jury of smothering and killing her four children over a 10-year period. Each child died suddenly and unexpectedly during a sleep period, at ages ranging from 19 days to 18 months. In 2019 we were asked to investigate if a genetic cause could explain the deaths, as part of an inquiry into the mother's convictions.

Methods and results: Whole genomes or exomes of the mother and her four children were sequenced. Functional analysis of a novel CALM2 variant was performed by measuring Ca2+-binding affinity, interaction with calcium channels and channel function. We found two children had a novel calmodulin variant (CALM2 G114R) that was inherited maternally. Three genes (CALM1-3) encode identical calmodulin proteins. A variant in the corresponding residue of CALM3 (G114W) was recently reported in a child who died suddenly at age 4 and a sibling who suffered a cardiac arrest at age 5. We show that CALM2 G114R impairs calmodulin's ability to bind calcium and regulate two pivotal calcium channels (CaV1.2 and RyR2) involved in cardiac excitation contraction coupling. The deleterious effects of G114R are similar to those produced by G114W and N98S, which are considered arrhythmogenic and cause sudden cardiac death in children.

Conclusion: A novel functional calmodulin variant (G114R) predicted to cause idiopathic ventricular fibrillation, catecholaminergic polymorphic ventricular tachycardia, or mild long QT syndrome was present in two children. A fatal arrhythmic event may have been triggered by their intercurrent infections. Thus, calmodulinopathy emerges as a reasonable explanation for a natural cause of their deaths.                                  _______________________________________________________________________

The tabloids in Australia called Kathleen Folbigg a murderer of innocent babies — the nation’s “worst female serial killer.” In 2003, a court sentenced her to 40 years in prison for smothering her four children before each had turned 2.

But all along, Ms. Folbigg has insisted that she is innocent, and that her children were all victims of Sudden Infant Death Syndrome.

Now, 90 leading scientists say they’re convinced she is right. New genetic evidence, the scientists say, suggests that the children died from natural causes, and they are demanding that she be pardoned.

In a petition sent to the governor of New South Wales last week, the group of scientists, which includes two Nobel laureates, called for Ms. Folbigg’s immediate release and an end to the “miscarriage of justice.”

The very public challenge sets up a tense standoff between some of the world’s top medical minds and a criminal court system that rarely overturns convictions. It’s a story of judges putting more weight on the ambiguous musings of a mother’s diary than on rare genetic mutations, and of scientists who are determined to make the legal system respect cutting-edge expertise.

Caught in the middle is Ms. Folbigg, who is now 53. More than 30 years after her first child’s death, her story has not changed, and she maintains that she will be vindicated.

A Troubled Mother and Her Children

Ms. Folbigg’s life has been troubled almost since the moment she was born.

She was just 18 months old when her father, Thomas Britton, murdered her mother in 1968. His wife had walked out on them over a money dispute. He stabbed her on a public footpath in Sydney in a drunken rage.

Roughly 28 years later, Ms. Folbigg wrote in her diary: “Obviously, I am my father’s daughter.”

By that point, in 1996, she had married a miner, Craig Folbigg, had moved to a working-class suburb, Newcastle, a coal capital north of Sydney, and had lost three of her children.

Ms. Folbigg’s first child, Caleb, died on Feb. 20, 1989, at 19 days of age. His death was classified by doctors as Sudden Infant Death Syndrome, or SIDS.

The next child, Patrick, died nearly two years later, at 8 months. He was blind and had epilepsy and choked to death, according to his death certificate.

A baby girl, Sarah, died on Aug. 30, 1993, at 10 months old, and her death was also classified as SIDS. Ms. Folbigg’s last child, Laura, died in March 1999 at 18 months old, with the cause initially listed as “undetermined.”

The deaths seemed at first to be simple, horrific tragedy. But Ms. Folbigg’s husband turned her in to the police after reading one of her diary entries. It said Sarah had left “with a bit of help.”

Ms. Folbigg told the authorities that what she wrote had simply captured the angst and despair of young motherhood and that “a bit of help” referred to her hope that God had taken her baby home.

At her trial, the doctor who had ruled Laura’s death as undetermined, Allan Cala, testified that he had never seen a case of four children dying in the same family. He was admitted as an expert witness, and though he did not present independent data, prosecutors relied on his account to argue that lightning strikes and flying pigs were more likely than four babies dying so young in the same family over a span of 10 years.

“There has never, ever been in the history of medicine any case like this,” one prosecutor said in closing arguments. “It is not a reasonable doubt, it is preposterous.”

The jury agreed. Ms. Folbigg, 35 at the time, was found guilty of the murders of Patrick, Sarah and Laura and the manslaughter of Caleb. She collapsed into tears as the verdicts were read.

The Science That Could Set Her Free

But there was never any medical evidence of smothering, the scientists say — that was one hole in the case. It’s the first thing mentioned in their pardon petition for Ms. Folbigg.

None of the children, they go on to say, were healthy when they died. Laura, the last to die, had been sick with a respiratory infection, and an autopsy later found an inflamed heart.

With those hints in mind, her lawyers asked geneticists to examine the case, searching for a mutation that might explain the family’s experience.

Carola Vinuesa, an immunologist from the Australian National University in Canberra, and another doctor, Todor Arsov, visited Kathleen in prison on Oct. 8, 2018, and received consent to sequence her genome. They both found that Ms. Folbigg had a rare mutation in what’s known as the CALM2 gene.

The genetic defect essentially creates heart arrhythmias that can cause cardiac arrest and sudden death in infancy and childhood.

Only about 75 people in the world are known to have the mutation, Professor Vinuesa said, including some parents without symptoms. But children died in at least 20 of those cases, and in many others, they suffered cardiac arrest.

That was especially true when there were triggers driving up adrenaline — and one known trigger is pseudoephedrine, a drug Laura was taking when she died.

Using blood and tissue samples from all four children, taken shortly after they were born, Professor Vinuesa and Dr. Arsov found that Sarah and Laura both had the same mutation as their mother.

By that point, Ms. Folbigg’s lawyers, who had already exhausted formal appeals, managed to secure a formal inquiry into the case. Professor Vinuesa submitted a lengthy report in December 2018.

But there were signs of resistance. Dr. Cala re-emerged, telling the judge that by the time Laura’s body arrived, after three deaths, you “have to have in the back of your mind, is there something else going on in relation to possible trauma?”

Bob Moles, a law professor at Flinders University, said that the admission of such statements showed a major flaw in Australian justice.

“One of the main problems we have is a willingness of courts to admit scientific evidence that is not really scientific,” he said.

Sensing that the evidence was not being taken seriously, Professor Vinuesa wrote to Peter Schwartz, a world-leading genetic researcher in Milan. He wrote back and said he had been studying a family in the United States with the same mutation, including two children who died from heart attacks.

He sent a letter to the inquiry with his findings. In July 2019, the judge reached a decision. He said that he had considered the scientific evidence but that he had found Ms. Folbigg’s diary quite compelling — and that he had no reasonable doubt about her guilt.

Refusing to Give Up

Frustrated but more determined, the scientists’ network gradually expanded.

Several of the people involved, including Dr. Arsov, submitted their findings to an international peer-reviewed journal. The paper was published in November.

Further research into Caleb’s and Patrick’s genomes has revealed that they had a separate rare genetic variant, which in studies with mice has been linked to early lethal epileptic fits.

In all, 90 eminent scientists have agreed that the medical evidence proves Ms. Folbigg’s innocence. The signatories to the pardon petition include Dr. Schwartz; John Shine, president of the Australian Academy of Science; and Elizabeth Blackburn, a 2009 Nobel laureate in medicine who teaches at the University of California, San Francisco.

“We would feel exhilarated for Kathleen if she is pardoned,” Professor Vinuesa said. “It would send a very strong message that science needs to be taken seriously by the legal system.”

by Damien Cave

https://www.nytimes.com/2021/03/08/world/australia/kathleen-folbigg-child-murder-genetics.html?referringSource=articleShare

Courtesy of a colleague

11 comments:

  1. https://www.youtube.com/watch?v=g9OrEcJcIDk

    https://www.youtube.com/watch?v=fAcEQpGiV5w

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  2. Ninety eminent scientists—including two Australian Nobel Laureates, medical practitioners, science leaders and prominent Australians—have signed a petition calling for Kathleen Folbigg’s immediate pardon and release from jail.

    Kathleen Folbigg was convicted and jailed in 2003 for murdering her children Patrick, Sarah and Laura and for the manslaughter of Caleb.

    The petition argues that Ms Folbigg should be granted a pardon based on the significant scientific evidence of natural causes of death for her children.

    The group submitted the petition to the Governor of NSW, the Honorable Margaret Beazley AC, earlier this week.

    The petition includes medical and scientific explanations from leading experts in their field that address each of the Folbigg children’s deaths.

    The petition concludes:

    The executive prerogative of mercy is designed to deal with failures of the justice system such as this one. It is incumbent on the Governor to exercise her power to stop the ongoing miscarriage of justice suffered by Ms Folbigg. Not to do so is to continue to deny Ms Folbigg basic human rights and to decrease faith in the New South Wales justice system.

    Ms Folbigg’s case also establishes a dangerous precedent as it means that cogent medical and scientific evidence can simply be ignored in preference to subjective interpretations of circumstantial evidence.

    Australian Academy of Science President, Professor John Shine AC PresAA FAHMS(Hon) FRS is among the petition’s signatories.

    “Given the scientific and medical evidence that now exists in this case, signing this petition was the right thing to do,” Professor Shine said.

    “These matters are incredibly complex. As our scientific knowledge deepens, so does the complexity, which makes the job of the courts a more complex one too.

    “We want to work more closely with the legal community to ensure evidence placed before courts is presented in the most accurate way possible, using the most appropriate experts and the most up-to-date science,” Professor Shine said.

    ANU Professor of Immunology Carola Vinuesa FAA FAHMS also signed the petition. She gave evidence to an inquiry into Ms Folbigg’s convictions and was asked to analyse the genomes of Kathleen and her four children in early 2019.

    “In all four Folbigg children, there is credible medical and pathological evidence, including new peer-reviewed genetic findings, by an international team of 27 scientists published in a top international cardiology journal last year, that points towards natural causes of death,” said Professor Vinuesa.

    “It is our responsibility as scientists to assist our legal peers so that they can rely on scientific, peer-reviewed evidence and ensure that domain experts are at their disposal to solve the issues of a difficult legal case.”

    Other petition signatories and Fellows of the Australian Academy of Science highlight below why they signed the petition.

    “It is deeply concerning that medical and scientific evidence has been ignored in preference of circumstantial evidence. We now have an alternative explanation for the death of the Folbigg children” – Child and public health researcher Professor Fiona Stanley AC FAA FAHMS(Hon) FASSA.

    “The science in this particular case is compelling and cannot be ignored. Despite the new knowledge gained from sequencing the human genome almost 20 years ago, we still have some way to go when it comes to both understanding the complexities of genetic disorders and educating the community about these issues” – Human geneticist and researcher Professor Jozef Gecz FAA FAHMS.

    “Expert advice should always be heard, and listened to. It will always trump presumption” – Former Chief Scientist Professor Ian Chubb AC FAA FTSE.

    https://www.science.org.au/news-and-events/news-and-media-releases/leading-scientists-call-folbigg-pardon

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  3. Although far from conclusive, new scientific evidence on the occurrence of SIDS, or cot death, in a family and the exonerations of mothers charged with murder over multiple cot deaths in their families, has indicated that the door may be slightly ajar for serial killer Kathleen Folbigg who was convicted of killing her four infants over a ten-year period.

    Based on this new evidence and in response to a petition presented by her supporters of 90 prominent doctors, professors and two Australian of the Year Recipients, an inquiry into the convictions of Kathleen Folbigg is currently being asked to be heard in the NSW Coroners Court.

    A few believe in Kathleen Folbigg’s innocence while many believe that she is arguably Australia’s most callous and despised murderess. In tonight’s Crime File we present the entire story. You judge for yourself.

    https://omny.fm/shows/nights/crime-file-mummy-dearest-the-crimes-of-kathleen-fo

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  4. Friends and supporters of Kathleen Folbigg have grave concerns for her safety after she was reportedly bashed by a fellow inmate in a horrific attack within days of transferring to another jail.

    The woman considered as Australia's worst female serial killer and 'most hated woman' was jailed in 2003 for the murders of her children Patrick, Sarah and Laura - aged from eight months to 19 months - between 1991 and 1999.

    She was also found guilty of the manslaughter of her first-born child, Caleb, who was just 19 days old when he died in Newcastle in 1989.

    Folbigg, 53 has maintained her innocence and now has the support of dozens of scientists and medical experts who have called for her to be pardoned from her 30-year jail term.

    She recently wrote to a pen pal recalling shocking details of the alleged New Year's Day attack which left her battered and bruised.

    Folbigg claimed in the letter the attack occurred within days of being transferred from Silverwater Jail in western Sydney to the new Clarence Correctional Centre on Grafton's outskirts in northern NSW.

    'In the first five days all my forward motion and hard work to be accepted in Main Pop(ulation) in Sydney was destroyed here,' she wrote in a letter to a friend obtained by The Australian.

    'I was ­assaulted on the 1st. Happy New Year to me. No real damage done. Purple eye, few bruises, all ­because the women didn't want "likes of me" in their unit,' she added in reference to her ‘baby killer’ and ‘killer mum’ image

    Folbigg's pen friend and other supporters now fear for her life, claiming she continues to suffer physical, emotional and psychological trauma behind bars.

    'I worry that she minimises all that she's going through and isn't getting the help she needs. She needs to be released now,' the friend told the publication.

    Folbigg says in her letter she was 'forced' to be relocated to the facility's protection wing, where she keeps herself busy maintaining the jail's grounds five mornings a week.

    She also expressed safety ­issues around the influx of 'marked inmates' arriving at the new correctional centre which opened eight months ago.

    Located 12.5 kilometres south-east of Grafton on a site covering the equivalent of 180 football fields, the state-of-an-art facility accommodates up to 1,700 inmates and will eventually become Australia's largest jail.

    Folbigg claims the alleged attack has undone her efforts to be accepted by fellow inmates at Silverwater, where she spent 17 years behind bars after she was sentenced in 2003.

    She was originally sentenced to 40 years' imprisonment, with a non-parole period of 30 years which was later reduced to 30 years, with a non-parole period of 25.

    Folbigg claims her friends also serving time there were also physically threatened if she stayed in the general compound.

    'I couldn't have that - wouldn't, so back at the beginning I am. It took me over 16 years to obtain some respect from staff and inmates and show them I am nothing like all the reports if you bother to get to know me. Here not even given the opportunity. Very sad,' Folbigg wrote.

    'But, I'm safe (as can be). So are my friends and that's all that matters really.'

    https://www.dailymail.co.uk/news/article-9335361/Kathleen-Folbigg-bashed-jail-friends-supporters-fear-life-bars.html

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  5. The name Kathleen Folbigg may not be familiar to Americans, but it surely is to Australians. The 53-year-old is known as the nation's "worst female serial killer" after being convicted of murdering her four babies in the 1990s, reports the Guardian. Folbigg, though, has always maintained her innocence, and now 90 scientists have signed a petition backing her up and calling for her to be pardoned. Folbigg blamed the deaths on Sudden Infant Death Syndrome, and the scientists agree that the infants almost certainly died of natural causes. Specifically, they blame genetic mutations, explains the New York Times. The researchers found that Folbigg an extremely rare mutation of a gene known as CALM2, as did two of her babies, Laura and Sarah. The defect has been known to trigger cardiac arrest and deaths among infants and older children.

    Folbigg's other two children, Caleb and Patrick, had different genetic mutations related to fatal epileptic seizures. “We would feel exhilarated for Kathleen if she is pardoned,” immunologist Carola Vinuesa of Australian National University tells the Times. “It would send a very strong message that science needs to be taken seriously by the legal system.” Vineusa lays out the research in the Conversation, adding that more such cases are likely to surface as science improves. Folbigg was convicted largely based on diary entries presented at her trial, including one in which she wrote that Sarah died "with a bit of help." Folbigg said it referred to her hope that God had taken her. Authorities are now considering the newly submitted petition from the scientists, two of whom are Nobel laureates. If the petition fails, Folbigg will be eligible to seek parole in 2028.

    https://www.newser.com/story/303430/australias-worst-female-serial-killer-may-be-innocent.html

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  6. Calmodulin is a protein that has many functions around the body, but the most important is to transport calcium around cells to convey cellular signals. This affects many different types of proteins and cellular processes. It helps muscle contraction, metabolism and even memory, so it’s an important protein.

    The protein is made by three genes that exist as a family: CALM1, CALM2 and CALM3. All make identical proteins, but the three genes working together create a quantity of calmodulin that is sufficient to carry out the calcium transport.

    As Paul Biegler explains, calmodulin is so important that tiny mutations in the genetic code can have severe effects in the protein, both at the level of a cell and that of a person’s health and heart.

    Kathleen Folbigg’s court case was in 2003, when research about calmodulin was a decade away. The first calmodulin mutations found to cause cardiac arrest were first discovered in 2012, where a whole Swedish family who had a history of such disease shared the N53I mutation in CALM1, which was inherited through a dominant allele that had a high chance of causing disease.

    In a 2013 report, two unrelated infants who experienced multiple cardiac arrests, as well as epilepsy and delayed neurodevelopment, had a mutation in either CALM1 or CALM2 that changed only a single amino acid.

    Likewise, in a 2016 study of two genetically unrelated children who experienced cardiac arrest, both had the CALM2 mutation N98S, where the asparagine (N) amino acid at position 98 changed to a serine (S). This was very similar to a CALM1 mutation, N97S, in a patient from Iraq that also had a disease related to cardiac arrest.

    Another mutation in CALM3 may have resulted in the deaths of two siblings at ages 5 and 4, as reported in 2019. That mutation – G114W – was the result of a nucleotide substitution that turned a glycine (G) amino acid at position 114 in the amino acid chain into a tryptophan (W) amino acid.

    This change meant that the small glycine in that position was turned into a bulky amino acid that repels water, thus altering the properties of calmodulin, too. This prevents the calcium from binding with the calmodulin properly, so the protein can’t perform its normal function.

    Another similar mutation in CALM2 called G114R, involved a substitution of a nucleotide, which altered the genetic code to carry information to make the amino acid at position 114 (the same gene position as the previous mutation) arginine (R) instead of glycine (G).

    This may seem small, but a glycine is an amino acid that holds no electrical charge and an arginine is positively charged, so the two have different properties. Overall, the mutant protein had less strength to bind to calcium and a lower ability to regulate the calcium channels it is normally involved in. (continued)

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  7. (continued) From such simple mutations, many processes that rely on the calmodulin are also disrupted, and there is a chain of poorly working cellular machinery. As the 2020 research paper showed, this could have led to cardiac arrest in Sarah and Laura Folbigg (also known as Child 3 and 4).

    On a larger scale, calmodulin mutations are not uncommon, and lead to disease and health issues called calmodulinopathies; these have symptoms such as cardiac arrest or heart rhythm problems (arrythmia), and, sometimes, infant and childhood death.

    Ultimately, calmodulin is a protein that is very sensitive to small mutations, which can have grave consequences.

    BSN bassoon

    The two other Folbigg children – Caleb and Patrick (Child 1 and 2) carried variants in the BSN gene.

    A 2003 study looked at the effect of a mutant bassoon protein, where part of the middle of the protein was missing. This meant that the gene, BSN, experienced a deletion mutation and some nucleotides were cut out. In turn, the amino acid chain that made the protein was missing a few amino acids and the whole protein was smaller.

    Much like cutting words out of a sentence but still putting it in the book, the protein is therefore missing some important components and is unlikely to work properly.

    The study found that mice who had this mutant version had recurring epileptic seizures, and 50% of mice with only mutant versions of the protein died before 6 months of age. Mice with normal versions of the protein, or both normal and mutant versions, did not experience these effects.

    Another 2018 study found that in a family of people who developed symptoms similar to palsy, all the individuals affected had mutation in the BSN gene. Unlike mice, individuals with both normal and mutant versions of bassoon were affected.

    They then identified that bassoon mutations were present in other people affected by a similar palsy, even though they were not related to the original family. These mutations had not been in gene databases, as there has been little data on the subject previously.

    When the researchers tested how bassoon functioned, they found that normal bassoon prevented accumulation of a protein called tau, which is a protein linked to Alzheimer’s. The mutant bassoon was unable to regulate these levels in the same way.

    The 2020 study found that the two male Folbigg children had a mutant version of BSN, and that Patrick (Child 2) also suffered severe epilepsy and blindness. Further investigation would be needed to establish a link between this mutation and the symptoms, because there are few studies on the clinical effects of BSN mutations to date.

    https://cosmosmagazine.com/biology/explainer-calmodulin/

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  8. “Manipulative” is how prison officers once described Kathleen Megan Folbigg, the convicted serial baby killer who has just cost the state of NSW millions trying – and failing – to prove her innocence.

    https://www.news.com.au/national/courts-law/inside-serial-baby-killer-kathleen-folbiggs-violent-and-tragic-life/news-story/39e2bbb4b7f8e2c9eacc29cce09094a7

    Behind bars in the country’s toughest maximum security women’s prison, Folbigg would manipulate other female inmates and try mental tricks with the prison officers.

    As Australia’s worst female serial killer, and a killer of babies, Folbigg endured a status as the most reviled type of offender and always claimed “I didn’t do it”.

    Unsurprisingly, behind bars this familiar assertion doesn’t cut the mustard.

    But on the outside, Folbigg managed to convince swathes of lawyers, scientists and doctors that she really didn’t kill her four infant children over the space of a decade.

    In perhaps her most manipulative act to date, Folbigg has managed to put whole factions of the legal fraternity at loggerheads.

    But on Wednesday, the NSW Court of Appeal found that “no error of law” had been made by the 2019 inquiry which found Folbigg’s conviction 18 years ago had been not only correct, but reinforced.

    Now it is likely the 53-year-old prison inmate will remain behind bars until her 2028 release.

    And she will walk out of prison only as a paroled criminal, not the cruelly wronged saint her supporters believe her to be.

    There’s no happy ending for Kathleen Folbigg’s violent and troubled life, which began as a baby when her father murdered her mother by stabbing her in the street.

    And there’s no pretending that the sinister words in Folbigg’s secret diaries weren't about her culpability in murdering three of her children and unlawfully killing the other.

    The diaries, which Folbigg claimed in 2019 were only about her struggling to cope with motherhood, included entries which said her infant daughter made her “snap her cog”.

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    1. https://www.news.com.au/national/courts-law/inside-serial-baby-killer-kathleen-folbiggs-violent-and-tragic-life/news-story/39e2bbb4b7f8e2c9eacc29cce09094a7

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  9. A woman who was convicted of smothering her four children has lost an appeal against an inquiry that concluded they had not died from natural causes.

    The New South Wales state Court of Appeal dismissed Kathleen Folbigg's application for a review of a judge's ruling that "makes her guilt of these offences even more certain"

    Scientists and doctors say Kathleen Folbigg is the victim of a "miscarriage of justice" as there is medical evidence to suggest the children died from natural causes, but others consider the deaths too tragic to be bad luck alone.

    A petition for a pardon was made this month to New South Wales governor Margaret Beazley, which would enable Folbigg's release, but her convictions would still stand.

    The petition carried the signatures of 91 scientists, medical practitioners and related professionals including two Nobel laureates.

    "Today's decision and the pardon petition have got many more people looking at this important case than ever before, and many people are starting to ask valuable questions about how we got here," her friend Tracy Chapman said in a statement.

    "Many international eyes are now on this case and there're many more Australians rightly asking why Kath's still in prison after 18 years when there's mounting scientific evidence relating to her innocence," the statement added.

    https://news.sky.com/story/kathleen-folbigg-mother-convicted-of-killing-her-four-children-loses-appeal-12255119

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  10. Convicted baby-killer Kathleen Folbigg has lost her bid to overturn the findings of a judicial inquiry that reinforced her guilt over the deaths of her four young childre the manslaughter or murder of her four children in 2003.

    The 53-year-old was sentenced to at least 25 years jail in 2003 over the manslaughter of her first child Caleb and the murder of three others, Sarah, Patrick and Laura.

    The children, aged between 19 days and 18 months, all died suddenly in the family's Newcastle home over a 10-year period and post-mortem examinations could not determine why they had stopped breathing.

    In 2018, the NSW Attorney-General ordered an inquiry into Folbigg's convictions after her legal team argued there was fresh medical evidence to suggest the babies may have died from natural genetic causes.

    Kathleen Folbigg was found guilty by a jury in 2003 for the manslaughter of one and murder of three of her children.(Supplied)
    The evidence involved gene sequencing showing two of the children had a genetic mutation that could have caused Sudden Infant Death Syndrome.

    But In 2019, the inquiry by the Honourable Reginald Blanch AM, QC, found there was no natural explanation for their deaths and reinforced Folbigg's guilt.

    In seeking to have the findings of the judicial review overturned, Folbigg's legal team argued that the judge "did not engage" with the consequences of the medical evidence and its impact on reasonable doubt.

    They also argued that he misinterpreted expressions of guilt that were contained in Folbigg's diary.

    In the judgement delivered, the Court of Appeal found "this was not a case in which the judicial officer's conclusion was at odds with the scientific evidence".

    It said the evidence provided only a "theoretical possibility" and found not all the victims shared the genetic abnormality.

    The court stated that when all the evidence was weighed up, including Folbigg's diary entries "there was an an ample basis" for the Judicial Inquiry to conclude there was no reasonable doubt as to her guilt.

    A recently released 14-page petition to the Governor of NSW, signed by 90 medical practitioners and science leaders, called for Folbigg's immediate pardon and release.

    https://www.abc.net.au/news/2021-03-24/kathleen-folbigg-appeal-bid-fails/100025722

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