Autism Epigenetics News Updates from the Escher Fund for Autism, July 2015
A Father Prenatally Exposed to Synthetic Hormones, a Son with Idiopathic Severe Mental Illness and Autism: Is Germline Epimutation to Blame?
[See our blog for the story. The author is the father of a nine year-old boy with multiple mental and developmental disabilities. He lives in California.]
• Chrissy's prenatal drug exposure story: A Glut of Abnormal Neurodevelopment in One Family — Did Grandma's 1960s Pregnancy Drugs Cause Germline Errors?
• Joan's prenatal drug exposure story: A Mother of Three Children with Autism Speaks Out About Her Prenatal Exposure to Synthetic Steroid Hormone Drugs
• Jill's prenatal drug exposure story: A Generation of Drugged DNA?
$25k RFP due June 30, 2015: Parental Germline Exposures in the Histories of Autism Multiplex Families
Autism is highly heritable without being "genetic" in the classic sense, and its rates are skyrocketing, up 28-fold in California's DDS system since 1987. We hypothesize that a subset of ASDs arise from induced epigenomic and/or genomic disruptions of parental germline during the vulnerable early phase of fetal germline synthesis.
This new RFP asks investigators to look at F2 ASD multiplex families to probe this idea, with an emphasis on ascertainment of F1 in utero pharmaceutical and other acute exposures, such as maternal smoking, in the 1950s, 60s, and 70s. RFP details can be found at: germlineexposures.org/grants.
New Papers in Cell Suggest Distinctive Epigenetic Treatment for Neurodevelopment Genes on Human Germline
It appears some areas of our DNA methylome are not entirely erased during gametogenesis. New research indicates that about five per cent of our genetic code carries molecular traces of past exposures, and may by leaving a devastating legacy for children and grandchildren.
Professor Azim Surani, from the Wellcome Trust/Cancer Research UK Gurdon Institute at the University of Cambridge, said: “The information needs to be reset in every generation before further information is added to regulate development of a newly fertilised egg. It’s like erasing a computer disk before you add new data."
But 5% of the genome are ‘escapee’ regions which contain some genes that are particularly active in neuronal cells, which may serve important functions during development.
Walfred Tang, a PhD student who is the first author on the study, said: “Our study has given us a good resource of potential candidates of regions of the genome where information is passed down not just to the next generation but potentially to future generations, too.”
See the paper in Cell: A unique gene regulatory network resets the human germline epigenome for development
Also published in Cell:
DNA Demethylation Dynamics in the Human Prenatal Germline
The Transcriptome and DNA Methylome Landscapes of Human Primordial Germ Cells
Worth a Watch: Epigenetics and Intergenerational Inheritance
Professor Marcus Pembrey (co-recipient of our recent grant on fetal germline effects of maternal smoking, with Professor Jean Golding) is featured in this new YouTube video, featuring Dr. Elizabeth Radford as well.
The Germline Disruption Hypothesis of Autism, in an Infographic
Reminder: Mini-grants Available, No Deadline
Mini-grants in the $250-$5,000 range are available on a rolling basis to support meetings, papers, research, or other work related to investigations of the induced germline disruption hypothesis of autism. Simply email us with your inquiry.
The Escher Fund for Autism supports projects that investigate the role of de novo germline perturbation in the etiology of autism and related disorders.
Visit GermlineExposures.org for:
• Expert Q&As
• Germline epigenetics in the news
• Germline development and reprogramming backgrounder
A Father Prenatally Exposed to Synthetic Hormones, a Son with Severe Mental Illness and Autism: Is Germline Epimutation at Work?
[The author is the father of a nine year-old boy with multiple mental and developmental disabilities. He lives in California.]
Our son, Jacob (not his real name), is nine years old. He has been diagnosed with a range of mental health and developmental disorders, including autism spectrum disorder, oppositional defiant disorder, mood disorder, anxiety disorder, and most tragically, childhood onset schizophrenia. In spite of multiple medication trials and behavioral and other therapies over many years, Jacob remains violent toward caregivers on a daily basis and less frequently toward peers. In addition, Jacob is chronically internally preoccupied and disconnected from reality, intermittently distressed by paranoia, delusions and the voices only he hears, and his thinking and speech have become so garbled that he is incoherent the vast majority of the time. In a meaningful sense, we have lost and continue to lose gradually the child we once thought we had.
Behind the diagnostic labels, the severity of his abnormal brain development and the impairments in his functioning are obvious. His violent behaviors have become so frequent and dangerous he can no longer live at home. No specialized school or residential treatment center in California—facilities designed to handle children with disabilities like these—would serve him, so we had to send Jacob to a placement 3,000 miles away, after he spent the majority of the last 16 months in hospital and partial hospital settings.
While my wife and I each have some very distant relatives with mental illness or autism, none of our 11 nieces and nephews nor any other close relatives have anything like the mental health or developmental challenges that Jacob does. Furthermore, Jacob's disorders are considered "idiopathic" in the sense that clinicians cannot find— despite extensive testing—any prenatal or genetic causes for this most unexpected, traumatic, and truly horrifying outcome in our son.
A few years ago, at the prompting of our friend Jill Escher, I asked my mother if I had been exposed in the womb to any fertility or anti-miscarriage treatments. I thought it was a strange question, but Jill had two children with idiopathic autism, and she explained she had just discovered that she had been exposed in utero to synthetic steroid hormone drugs via injections given to her mother at a popular Los Angeles fertility clinic. In Jill's case, her mother had two prior miscarriages and the practitioners of the time felt that supplementing a pregnancy with synthetic hormone cocktail could improve the gestational environment. Jill thought those old drugs could have disrupted the molecular programming of her eggs.
So I asked my mother, and the answer, to my surprise, was yes.
I was born in 1969 in New York City, and while pregnant with me my mom received treatments at the New York Fertility Institute, but did not recall the names of the drugs used. They treated her with hormones because she had had a D&C due to endometriosis. Though she could not locate those medical records, she said, "I remember taking some injections during the first few months of pregnancy so as not to miscarry."
Whether my prenatal exposures to some form of anti-miscarriage hormone protocol of the 1960s affected the development of my gametes, I cannot say for certain. But it's a hypothesis that maps to the emerging research demonstrating adverse fetal germline effects of endocrine-disrupting drugs, and the revelation that the genes most likely to retain epimutations during reprogramming are those involved with neurodevelopment.
I hope the tragedy of our son, and that of Jill's autistic children, too, will help prompt more researchers to tackle the germline disruption hypothesis. These "genetic-ish" conditions must be seen in light of actual biological history. These old prenatal exposures to powerful chemical compounds used in obstetric practice were very real and very acute, even if you did not ask or know about them.
Jill Escher, Escher Fund for Autism, is a California-based science philanthropist and mother of two children with severe autism, focused on the question of how environmentally induced germline disruptions may be contributing to today's epidemics of neurodevelopmental impairment. You can read about her discovery of her intensive prenatal exposure to synthetic hormone drugs here. Jill is also president of Autism Society San Francisco Bay Area.