Joint Chinese-UK study shows Levels similar to the West
The first large-scale study of autism in China has revealed that around one in a hundred people in the country has an autism spectrum condition – the same figure as found in the West.
The research was carried out by an international team of researchers from the University of Cambridge, UK, and the China Disabled Persons’ Federation and Chinese University of Hong Kong. It is the result of an international partnership launched in 2013.
Autism spectrum conditions – which include autism and Asperger’s syndrome – are characterised by impairments in social interaction and communication, alongside the presence of unusually repetitive behaviour and narrow interests, difficulties adjusting to unexpected change, and sensory hyper-sensitivity.
Autism was first described in Western cultures, and only later recognised in Asian countries. Around one in 100 school age children in the UK is autistic, but autism prevalence in China has been reported to be lower than in the West. The reasons for this difference are that most studies in China have only included the special school population, overlooking the mainstream school population; and that most studies in China have not used validated and reliable screening and diagnostic methods.
“Understanding the prevalence of autism is important because of its relevance to planning services to support those living with the condition, as well as their families,” said Professor Carol Brayne from the Cambridge Institute of Public Health.
Professor Simon Baron-Cohen, Director of the Autism Research Centre in Cambridge (ARC) added: “We need to study autism outside Western populations, since most of the research to date has only been carried out in the West. This collaboration with colleagues in China is so valuable to help us understand what is universal and what is culture-specific in autism research.”
To address the gap in understanding autism in China, the researchers tested the total autism prevalence in mainstream and special schools in Jilin City, and mainstream school autism prevalence in Jiamusi and Shenzhen cities. They screened children aged 6 to 10?years old in the three cities using the Childhood Autism Screening Test (or CAST), a 37-item questionnaire, completed by parents, and developed and validated by the Cambridge team. The questionnaire gives a score of 0 to 31, and children scoring 15 or above were then given a clinical assessment. The results are published in the journal Molecular Autism.
In Jilin City, from a total population of 7,258, the team identified 77 cases of autism, equating to a prevalence of 108 per 10,000, very similar to that found in the West.
In Shenzhen and Jiamusi cities, only data for children in mainstream education was available; in Shenzhen City, 42 out of every 10,000 children in mainstream education had autism, and in Jiamusi City this figure was 19 per 10,000. In all three cities, the researchers identified new cases of autism in mainstream schools, confirming that there is under-diagnosis of autism in China.
“Contrary to previous studies, we have shown that the prevalence of autism spectrum conditions in China is in line with that found in the West,” said Dr Sophia Xiang Sun, who conducted this study as part of her PhD at Cambridge University and who is now based in the Star Kay Bridge Research Centre for Children with Autism in Xiamen, China.
Professor Patrick Leung, from the Chinese University of Hong Kong, said: “Previous research into the autism spectrum in China has mainly focused on the most severe subtype, childhood autism. We have been able to use a standardised screening methodology, allowing us to compare the results with Western countries to show that autism occurs broadly at the same rate, irrespective of culture.”
Dr Carrie Allison, from the Cambridge Autism Research Centre, commented: “Completing this study with colleagues in China has been nothing short of remarkable. It has involved translating Western autism screening instruments into Chinese, training Chinese clinicians in autism diagnosis, and working with national Chinese agencies, screening in three Chinese cities.”
Professor Fiona Matthews, the statistician on the Cambridge team and now based in Newcastle University, noted: “A strength of this study is the near universal response rate that is possible in China, which we rarely achieve in the West, making the epidemiology far more representative.”
The research was funded by the Autism Research Trust, the NIHR CLAHRC for East of England, the Chinese University of Hong Kong (CUHK), and the Medical Research Council UK.
Breakthrough research demonstrating that children with autism as young as 18 months can vastly improve their language, cognition and social skills with an early intervention developed by UC Davis Professor Sally Rogers has been replicated in a major new study.
Rogers, a professor of Psychiatry and Behavioral Sciences at the MIND Institute, began work on a novel developmental approach to autism in Denver in 1981, and in partnership with her colleague and co-author Geraldine Dawson developed an approach to improving long-term outcomes for very young children. The Early Start Denver Model has since become a method used throughout the U.S. and around the world.
But until now ESDM had not been tested in the most rigorous fashion − a multi-site randomized trial, comparing the approach with community-based autism interventions. The study, which appears today in Journal of theAmerican Academy of Child and Adolescent Psychiatry, began in 2007 at three university sites around the country. The new research replicates an ESDM study published in 2010. Rogers emphasized that replication studies are rare and costly but critical to validate novel scientific findings.
The new study found that children receiving intensive ESDM in their homes for an average of 15 hours per week made significantly greater language gains than did children in the community interventions, and this was true for both children with more severe delays and those with less.
In addition to validating the efficacy of ESDM for language development, the study also found that children receiving services in the community settings made large gains in several areas.
“The idea that little children with autism who are getting good treatment can make this much IQ and language gain means we should expect this from quality early-intervention experiences,” Rogers said. “These findings should raise families’ hopes a whole lot.”
Pioneering autism treatment was a new idea
What distinguishes ESDM from the more traditional, behavioral interventions used with children with autism is that it combines developmental and behavioral approaches and is carried out within in everyday routines. ESDM is built on moment-to-moment interactions that young children typically have with other people, especially their parents, and uses children’s interests and favorite activities to assure that social interaction is interesting and fun.
“Unlike other approaches popular at the time that the Denver Model began, we used a typical preschool physical environment and focused on the learning opportunities that existed in social interactions between children and adults to accelerate children’s development,” Rogers said. “This was a new idea at the time.”
In 2012, TIME magazine named ESDM one of the top 10 medical breakthroughs because their work demonstrated that brain function among young children with autism can normalize with effective early intervention in profound, enduring ways.
For the current study 118 children with autism, ages 14 months to two years, were enrolled and randomly assigned to either ESDM or community interventions for 27 months. Children assigned to ESDM intervention received three months of weekly parent coaching followed by 24 months of one-on-one treatment about 15 hours per week in homes or daycare settings from supervised therapy assistants. Parents received coaching four hours monthly from a certified ESDM therapist. In the community setting, hours of treatment varied by site.
What researchers found was that at two of the three sites, children receiving ESDM had significantly more language improvement than the children in the community interventions, and there was no significant difference in language gain at the third site between the two modalities. When results from all three sites were pooled, there was a significant advantage for the children in the ESDM group overall.
“Language is the bridge to learning,” Rogers said. “Language is the door that opens up social communication and education and interactions with people in your community. It’s how you share with people. It’s a main vehicle for social interaction once you pass infancy.”
Autism treatment in the community greatly improved over time
The study also found that in terms of cognition and social skills, both the ESDM and community treatment groups made significant gains. Fortunately, Rogers said, laws requiring insurance coverage for early autism intervention and new knowledge about effective treatment have greatly improved community options for families seeking help for young children diagnosed with autism.
Rogers said families with a child diagnosed with autism should take some comfort knowing that the early treatments now widely available do make a difference.
“It says the autism scores at the time of diagnosis are just a starting point,” she said. “It says that the developmental paths and learning capacity of young children with autism are more plastic than we knew, and there are many ways to get learning opportunities to them.”
In addition to Rogers, UC Davis authors on the study were Marie Rocha, Laurie Vismara and Meagan Talbott. Other co-authors on the study included: Annette Estes and Jessica Greenson of the University of Washington; Catherine Lord and Jamie Winter of Weill Cornell Medicine, Cornell University; Costanza Colombi of University of Michigan; Geraldine Dawson of Duke University, and Gerhard Hellemann of UCLA.
This study was supported by individual Autism Speaks grants to Annette Estes and to Sally Rogers and by NIMH/NICHD award number R01 081757 as part of the Autism Centers of Excellence (ACE) Treatment Network, clinicaltrials.gov identifier NCT 00698997.
In recent days there has been significant coverage surrounding the Boca Raton native becoming the first openly autistic person to be admitted to the Florida bar. This accomplishment being widely accepted is a huge stride for those diagnosed with autism and autism professionals working hard to create inclusive workplaces.
To help others understand why inclusivity and supporting those with disorders is so important, I’d like to offer Arianna Esposito, Associate Director of Adult & Transition Programs at the Kinney Center for Autism Education and Support at Saint Joseph’s University. She is able to offer tips to help employers create an inclusive workplace. These tips are not only helpful for individuals with autism, but can benefit all employees. Please see a sampling of her advice below:
Fluorescent lights can be extremely bothersome for someone with sensory challenges. Offering dimmer lighting options or access to natural light are good alternatives. Odorless office supplies, cleaning supplies and other products are recommended to have in a supply closet or open areas. Designated, private quiet rooms for employees to take a call in or do work are a great option.
Providing clear and specific feedback is important for an inclusive structure. Try putting a positive spin on code of conduct by turning “do not” rules into “can do” rules.
Being flexible with needs such as accepting requests to wear specific clothing items and seating locations (not near crowded areas) will help individuals navigate the social world.
The rate of diagnosis for autism spectrum disorders (ASD) is the same among all racial groups — one in 110, according to current estimates. However, a study by a Florida State University researcher has found that African-American children tend to be diagnosed later than white children, which results in a longer and more intensive intervention. The reasons for later diagnoses include a lack of access to quality, affordable, culturally competent health care, according to Martell Teasley, an associate professor in Florida State’s College of Social Work who has conducted a comprehensive review of researchliterature on autism and African-American children. In addition, the stigmaattached to mental health conditions within the black community contribute to misdiagnoses of autism, and underuse of available treatment services.
“There are no subjective criteria for diagnosing autism. Only brain scans can truly provide appropriate diagnoses, because we are dealing with biological and chemical imbalances in the brain,” Teasley said. “Not every child is going to have access to this kind of medical evaluation, particularly those who are indigent and don’t have health care funding.”
Teasley examined ASD diagnosis and treatment strategies, and their effect on African-American families, in “Autism and the African-American Community,” a paper published in a special issue of the journal Social Work in Public Health (Vol. 26, Issue 4, 2011) that dealt with health-care policy issues in the black community related to the human genome.
Teasley co-wrote the paper with Ruby Gourdine, a professor of social work at Howard University in Washington, D.C., and Tiffany Baffour, an associate professor of social work at Winston-Salem State University in North Carolina. Because of the social stigma, Teasley says that some African-American families might be resistant to accept a diagnosis and treatment. “Less discussion about autism among African-Americans or between African-Americans and health care providers leads to misdiagnoses, a lack of treatment and a lack of services,” Teasley said.
“This will lead to greater challenges for families — more stress and anxiety, and poorer developmental outcomes.” African-Americans also might resist a diagnosis and treatment because of a mistrust of mainstream health care providers over past discrimination. “African-Americans are well versed in going to a doctor who might have biases or discriminatory practices, so they may not readily accept what a doctor says,” Teasley said. In addition, a cultural divide between African-Americans and mainstream health care providers can hinder a timely and correct diagnosis.
“There are not enough health care professionals who understand the cultural norms and attributes of the African-American community,” Teasley said. African-Americans live in all types of settings, but the majority live in urban areas, which have seen a decline in the number of mental-health care agencies since the 1980s. “This lack of accessibility causes a problem for some African-Americans,” Teasley said. Once a child is diagnosed with ASD, Teasley says both the child and the members of his or her family needs to receive appropriate training and counseling. “The children need behavioral counseling so they can develop the skills to live as independently as possible,” he said. “The families need to learn how to work with children who are autistic. “Intervention for any autistic child needs to start around age 3, so we can get the child to begin to learn how to eat right and develop normal, healthy routines, which will result in a better developmental outcome,” Teasley said. “Later intervention will result in a poorer developmental outcome that can have a lasting impact on the child’s and family’s quality of life.”
Ten Signs of Possible Autism-Related Delays in 6- to 12-Month-Old Children
Though autism is often not diagnosed until the age of three, some children begin to show signs of developmental delay before they turn a year old. While not all infants and toddlers with delays will develop autism spectrum disorders (ASD), experts point to early detection of these signs as key to capitalizing on early diagnosis and intervention, which is believed to improve developmental outcomes.
According to Dr. Rebecca Landa, director of the Center for Autism and Related Disorders at the Kennedy Krieger Institute in Baltimore, Md., parents need to be empowered to identify the warning signs of ASD and other communication delays. “We want to encourage parents to become good observers of their children’s development so that they can see the earliest indicators of delays in a baby’s communication, social and motor skills,” says Dr. Landa, who also cautions that some children who develop ASD don’t show signs until after the second birthday or regress after appearing to develop typically.
For the past decade, Dr. Landa has followed infant siblings of children with autism to identify red flags of the disorder in their earliest form. Her research has shown that diagnosis is possible in some children as young as 14 months and sparked the development of early intervention models that have been shown to improve outcomes for toddlers showing signs of ASD as young as one and two years old. Dr. Landa recommends that as parents play with their infant (6 – 12 months), they look for the following signs that have been linked to later diagnosis of ASD or other communication disorders: 1. Rarely smiles when approached by caregivers2. Rarely tries to imitate sounds and movements others make, such as smiling and laughing, during simple social exchanges3. Delayed or infrequent babbling4. Does not respond to his or her name with increasing consistency from 6 – 12 months 5. Does not gesture to communicate by 10 months6. Poor eye contact7. Seeks your attention infrequently8. Repeatedly stiffens arms, hands, legs or displays unusual body movements such as rotating the hands on the wrists, uncommon postures or other repetitive behaviors9. Does not reach up toward you when you reach to pick him or her up10. Delays in motor development, including delayed rolling over, pushing up and crawling
“If parents suspect something is wrong with their child’s development, or that their child is losing skills, they should talk to their pediatrician or another developmental expert,” says Dr. Landa. “Don’t adopt a ‘wait and see’ perspective. We want to identify delays early in development so that intervention can begin when children’s brains are more malleable and still developing their circuitry.”
About the Kennedy Krieger InstituteInternationally recognized for improving the lives of children and adolescents with disorders and injuries of the brain and spinal cord, the Kennedy Krieger Institute in Baltimore, MD serves more than 16,000 individuals each year through inpatient and outpatient clinics, home and community services and school-based programs. Kennedy Krieger provides a wide range of services for children with developmental concerns mild to severe, and is home to a team of investigators who are contributing to the understanding of how disorders develop while pioneering new interventions and earlier diagnosis. For more information on Kennedy Krieger Institute, visit: www.kennedykrieger.org.
Black and Hispanic children are most at risk for missed autism diagnosis, according to a Rutgers researcher
One-fourth of children under age 8 with autism spectrum disorder — most of them black or Hispanic — are not being diagnosed, which is critical for improving quality of life.
The findings, published in the journal Autism Research, show that despite growing awareness about autism, it is still under-diagnosed, particularly in black and Hispanic people, said study co-author Walter Zahorodny, an associate professor at Rutgers New Jersey Medical School and director of the New Jersey Autism Study, which contributed to the research.
Researchers analyzed the education and medical records of 266,000 children who were 8 years old in 2014, seeking to determine how many of those who showed symptoms of the disorder were not clinically diagnosed or receiving services.
Of the nearly 4,500 children identified, 25 percent were not diagnosed. Most were black or Hispanic males with deficits in mental abilities, social skills and activities of daily living who were not considered disabled.
“There may be various reasons for the disparity, from communication or cultural barriers between minority parents and physicians to anxiety about the complicated diagnostic process and fear of stigma,” Zahorodny said, “Also, many parents whose children are diagnosed later often attribute their first concerns to a behavioral or medical issue rather than a developmental problem.”
Screening all toddlers, preschool and school-age children for autism could help reduce the disparities in diagnosis, Zahorodny said. In addition, clinicians can overcome communication barriers by using pictures and/or employing patient navigators to help families understand the diagnosis process, test results and treatment recommendations.
States can help improve access to care by requiring insurance companies to cover early intervention services when a child is first determined to be at risk rather than waiting for a diagnosis, he said.
The research was conducted through the Autism and Developmental Disabilities Monitoring Network, a surveillance program funded by the U.S. Centers for Disease Control and Prevention that tracks the prevalence of the developmental disorder in 11 states: Arizona, Arkansas, Colorado, Georgia, Maryland, Minnesota, Missouri, New Jersey, North Carolina, Tennessee and Wisconsin.
Imperceptible variations in movement patterns among individuals with autism spectrum disorder are important indicators of the severity of the disorder in children and adults, according to a report presented at the 2014 Society for Neuroscience annual meeting in November.
For the first time, researchers at Indiana University and Rutgers University report developing a quantitative way to assess these otherwise ignored variations in movement and link those variations to a diagnosis.
“This is the first time we have been able to explicitly characterize subtypes of severity in autism spectrum disorder,” said Jorge V. José, Ph.D., vice president of research at Indiana University and the James H. Rudy Professor of Physics in the IU Bloomington College of Arts and Sciences. “We also have determined that a pattern exists in the movement variations in some cases between children with autism and their parents, leading us to surmise that genetics plays a role in movement patterns.”
In a blinded study, José, who also is a professor of cellular and integrative physiology at the IU School of Medicine, and co-principal investigator Elizabeth B. Torres, Ph.D., an assistant professor in the Department of Psychology in the School of Arts and Sciences at Rutgers University, attached high-sensitivity movement sensors to the arms of study participants to track their micro-movements as they extended and retracted their hand to touch a specific spot on a touch screen.
Using analytics they developed, Drs. José and Torres, together with Di Wu, a Ph.D. graduate student in José’s lab in the physics department at IU Bloomington, evaluated the local spikes in speed — traditionally considered as noise in the data. The sensors recorded 240 movements per second for the 30 people with autism, eight healthy adults and 21 parents of children with autism tested. The participants were asked to touch a spot on a screen moving continuously about 100 consecutive times.
“These variations in the hand’s movement speed produced a pattern that clustered in specific regions of a graph that produced metrics we could use — not only in children with autism but in their parents,” Dr. Torres said. “People with autism are known to have problems with sensing their body motions and sensing their body in general. Our earlier research proved that the random patterns of their speed were significant. What we did not expect was to find random, minute speed fluctuations during the intentional action itself, much less identify this form of intentional tremor in some of their parents.”
That finding was part of the report presented by Wu at the 2014 Society for Neuroscience meeting in November attended by more than 32,000 scientists.
“In healthy adults, the minute fluctuations in the speed of their movements, which we call peripheral spikes or p-spikes, normally occur at the onset or at the end of the arm extension exercise,” Wu said. “They show very few p-spikes during the actual action, as the hand speeds up or slows down en route to the target. However, healthy children in the 3-to-5-year-old range have random patterns of p-spikes, as do adults and children with autism spectrum disorder.”
What this suggests, the researchers said, is that p-spikes normally become more organized with age in typically developing individuals. But, in children and adults with autism, the p-spikes remained random. The researchers tested people with autism between the ages of 3 and 30 and identified an absence of transition that typically developing children undergo after 4 or 5 years of age.
The researchers also tested 14 mothers and seven fathers who have a child with autism. When evaluating the noise from the data produced from the parents, the researchers were surprised to find that some of the parents had random p-spikes clustering in the graph similar to that of their children.
“This finding suggests that genetics may play a role in p-spike patterns,” Wu said. “We will need to further explore this result in other populations with neurodevelopmental disorders of known genetic origins and their family to better understand the surprising findings.”
Drs. José and Torres said the p-spike patterns are useful in determining severity of the disorder.
“Normally, children get more coordinated as they age, but we found that the young children with autism and the adults with autism all produced random p-spikes showing that they do not transition as they develop,” Dr. José said. “We also found a correlation between the randomness of the p-spikes and the severity of the autism disorder. Among those with autism, the more random their p-spikes, the lower spoken language ability they had overall.”
This research was funded by National Science Foundation Cyber-Enabled Discovery and Innovation Type I (Idea), grant number 0941587 — “A novel quantitative framework to study lack of social interactions in Autism Spectrum Disorders” — and by the New Jersey Governor’s Council for Medical Research and Treatment of Autism, grant number CAUT14APL018 — “New objective autism inventory to quantify peripheral plasticity during standard ADOS-2 social exchange.”
Brain Enlargement in Autism Due to Brain Changes Occurring Before Age 2
CHAPEL HILL, N.C. – In 2005, researchers from the University of North Carolina at Chapel Hill found that 2-year-old children with autism have brains up to 10 percent larger than children of the same age without autism.
Now a follow-up study by UNC researchers has found that the children who had enlarged brains at age 2 continued to have enlarged brains at ages 4 and 5, but the amount of the enlargement was to the same degree found at age 2. This increased brain growth did not continue beyond 2 years of age and the changes detected at age 2 were due to overgrowth prior to that time point. In addition, the study found that the cortical enlargement was associated with increased folding on the surface of the brain (or increased surface area) and not an increase in the thickness of outer layer of the brain (or gray matter).
“Brain enlargement resulting from increased folding on the surface of the brain is most likely genetic in origin and a result of an increase in the proliferation of neurons in the developing brain,” said Heather Cody Hazlett, PhD, assistant professor in the Department of Psychiatry, who is the lead author of the new study, which is published in the May 2011 issue of Archives of General Psychiatry.
In both the 2005 study and the new study, Hazlett and colleagues analyzed magnetic resonance imaging (MRI) scans of the children’s brains using computer software developed for that purpose by Martin Styner, PhD, an assistant professor of computer science and psychiatry at UNC, and Guido Gerig, PhD, formerly at UNC and now at the University of Utah.
“From earlier work by our group on head circumference or head size in children with autism, we think that brain overgrowth in many children with autism may actually be happening around the first birthday. Together these findings suggest that we should be searching for genes that may underlie the over-proliferation of neurons in this early post-natal period,” said Joseph Piven, MD, senior author of the new study and director of the Carolina Institute for Developmental Disabilities.
UNC is currently leading two separate studies aimed at that goal. Hazlett leads the Brain Development in School Age Children with Autism study, which is funded by Autism Speaks. “It was important to continue to follow these children to track their brain development to see if the brain and behavioral differences we observed were maintained as the children matured,” said Hazlett.
UNC is also leading the Infant Brain Imaging Study (IBIS), a National Institutes of Health-funded multi-center study which includes four sites around the U.S. “We are studying infant children at high genetic risk for autism, by virtue of their having an older brother or sister with autism – somewhere around 20 percent of those children will develop autism. We are doing brain scans and behavior assessments on those children at 6, 12 and 24 months of age to look at how the brain develops in the subgroup that develop autism before they have symptoms of autism at 6 months of age and over the interval that they develop autism – between 6 and 24 months of age, in most cases,” Piven said. “We are also looking at whether specific gene alterations may be responsible.”
Authors of the May 2011 article in Archives of General Psychiatry, in addition to Hazlett, are Michele Poe, PhD, Guido Gerig, PhD, Martin Styner, PhD, Chad Chappell, Rachel Gimpel Smith, Clement Vachet, MS, and Piven.
The UNC authors are all affiliated with one or more of the following: The Department of Psychiatry in the School of Medicine, the Carolina Institute for Developmental Disabilities, the Frank Porter Graham Child Development Institute, and the Department of Computer Science in the College of Arts and Sciences.
Spontaneous mutations in paternal sperm are linked to autism spectrum disorder; researchers have developed way to quantify those mutations and assess chances the mutations will cause disease.
The causes of autism spectrum disorder or ASD are not fully understood; researchers believe both genetics and environment play a role. In some cases, the disorder is linked to de novo mutations that appear only in the child and are not inherited from either parent’s DNA.
In a study published December 23, 2019 in Nature Medicine, an international team of scientists, led by researchers at University of California San Diego School of Medicine, describe a method to measure disease-causing mutations found only in the sperm of the father, providing a more accurate assessment of ASD risk in future children.
“Autism afflicts 1 in 59 children and we know that a significant portion is caused by these de novo DNA mutations, yet we are still blind to when and where these mutations will occur,” said co-senior author Jonathan Sebat, PhD, professor and chief of the Beyster Center for Molecular Genomics of Neuropsychiatric Diseases at UC San Diego School of Medicine. “With our new study, we can trace some of these mutations back to the father, and we can directly assess the risk of these same mutations occurring again in future children.”
Recent studies suggest gene-damaging de novo mutations are involved in at least 10 to 30 percent of ASD cases, with the number of mutations rising with the father’s age at time of conception. De novo mutations occur spontaneously in parents’ sperm or eggs or during fertilization. The mutation is then present in each cell as the fertilized egg divides. Studies now point to male sperm as a particularly important source of these mutations, with the chance of the mutation recurring within the same family generally estimated at 1 to 3 percent.
“However, such estimates are not based on actual knowledge of the risk in an individual family, but instead are based on frequencies in the general population,” said co-senior study author Joseph Gleeson, MD, Rady Professor of Neuroscience at UC San Diego School of Medicine and director of neuroscience research at the Rady Children’s Institute for Genomic Medicine. “When a disease-causing mutation occurs for the first time in a family, the probability that it could happen again in future offspring is not known. Thus families must make a decision with a great deal of uncertainty.”
For their study, Gleeson, Sebat and colleagues analyzed the sperm of eight fathers who were already parents of children with ASD. The goal was to look for the presence of multiple, genetically different material in cells in the same person, a phenomenon called mosaicism. Using deep whole genome sequencing, they found variants in offspring that were matched only in the fathers’ sperm.
“While medical textbooks teach us that every cell in the body has an identical copy of DNA, this is fundamentally not correct. Mutations occur every time a cell divides, so no two cells in the body are genetically identical,” said first author Martin Breuss, PhD, an assistant project scientist in Gleeson’s lab.
“Mosaicism can cause cancer or can be silent in the body. If a mutation occurs early in development, then it will be shared by many cells within the body. But if a mutation happens just in sperm, then it can show up in a future child but not cause any disease in the father.”
The researchers determined that disease-causing mutations were present in up to 15 percent of the fathers’ sperm cells, information that could not be determined through other means, such as blood samples.
“My laboratory has a long-standing interest in understanding the origins of pediatric brain disease, and how mutations contributes to disease in a child,” said Gleeson. “We previously showed that mosaicism in a child can lead to diseases like epilepsy. Here, we show that mosaicism in one of parents is at least as important when thinking about genetic counseling.”
If developed into a clinical test, the researchers said fathers could have their sperm studied to determine their precise risk of recurrence in future children. The methods might also be applied to men that haven’t had children yet, but who want to know the risk of having a child with a disease.
Co-authors include: Danny Antaki, Morgan Kleiber, Oanh Hong, Madhusudan Gujral, William M. Brandler, Ileena Mitra, and Melissa Gymrek, UC San Diego; Renee D. George, Kiely N. James, Laurel L. Ball, Xiaoxu Yang, Sara A. Wirth, Jing Gu, Camila A. B. Garcia, Damir Musaev, An Nguyen, Jennifer McEvoy-Venneri, and Evan Sticca, Howard Hughes Medical Institute at UC San Diego and Rady Children’s Institute for Genomics of Psychiatric Diseases; Renatta Knox, Howard Hughes Medical Institute at UC San Diego, Rady Children’s Institute for Genomics of Psychiatric Diseases and Weill Cornell Medical College; Martha Cristina Cancino Botello and Javiera Uribe Fenner, Hospital Universitari Mutua de Terrassa, Spain; Maria Cárcel Pérez, Maria Arranz, and Amaia Hervás, Fundacio Docencia i Recerca Mutua Terrassa, Spain; Andrea B. Moffitt and Zihua Wang, Cold Spring Harbor; and Orrin Devinsky, New York University School of Medicine.
Funding for this research came, in part, from EMBO Long-Term Fellowship (ALTF 174-2015), the Marie Curie Actions of the European Commission (LTFCOFUND2013, GA-2013-609409), Erwin Schrödinger Fellowship by the Austrian Science Fund (J 4197-B30), the National Institutes of Health (U01MH108898, R01NS083823, MH076431, MH113715), the Simons Foundation Autism Research Initiative, the Howard Hughes Medical Institute, the Silverman Family Foundation and Finding A Cure for Epilepsy and Seizures.
Disclosure: Martin Breuss, Danny Antaki, Morgan Kleiber, Kiely N. James, William M. Brandler, Jonathan Sebat and Joseph Gleeson are inventors on a provisional patent (PCT Ref. No. SD2017-181-2PCT) filed by UC San Diego and titled “Assessing risk of de novo mutations in males.”