Tag: ASD

Mutations in Sperm May Reveal Risk for Autism

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Credit: Martin Breuss, UC San Diego Health
In this illustration of sperm mosaicism, mutated sperm are depicted in red.

Researchers Use SDSC’s ‘Comet’ Supercomputer to Analyze Genome Sequences

While the causes of autism spectrum disorder (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 recent study published 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.

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“Autism afflicts one 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, 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.”

The research team used the Comet supercomputer based at the San Diego Supercomputer Center, an Organized Research Unit of UC San Diego, to align the whole genome sequences. “We called variants on the sequences and also detected de novo variants using Comet for these samples,” explained Danny Antaki, a UC San Diego Neurosciences postdoctoral scholar. “In short, Comet provided the foundation for the larger experiment as we were able to find the de novos that we wanted to analyze in sperm with the data generated on the supercomputer.”

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, 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,” said first author Martin Breuss, an assistant project scientist in Gleeson’s lab. “Mutations occur every time a cell divides, so no two cells in the body are genetically identical. 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 contribute 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.

About UC San Diego Health

UC San Diego Health, comprising a comprehensive health system throughout San Diego County, UC San Diego School of Medicine and Skaggs School of Pharmacy and Pharmaceutical Sciences, is one of five academic medical systems within the University of California system. We are committed to improving patient care while also researching new treatments and training tomorrow’s doctors and pharmacists. For more than 50 years, our renowned clinicians and scientists have made advances in numerous fields, including minimally invasive surgeries, personalized cancer therapy, cardiovascular treatment and surgery, transplantation and the early detection of autism.

About SDSC

As an Organized Unit of UC San Diego, SDSC is considered a leader in data-intensive computing and cyberinfrastructure, providing resources, services, and expertise to the national research community, including industry and academia. SDSC supports hundreds of multidisciplinary programs spanning a wide variety of domains, from earth sciences and biology to astrophysics, bioinformatics, and health IT. SDSC’s petascale Comet supercomputer is a key resource within the National Science Foundation’s XSEDE (eXtreme Science and Engineering Discovery Environment) program.

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Handwriting Is Real Problem for Children with Autism

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Photo by Hannah Olinger

Handwriting skills are crucial for success in school, communication, and building children’s self-esteem.

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The first study to examine handwriting quality in children with autism spectrum disorders (ASD) has uncovered a relationship between fine motor control and poor quality of handwriting in children with ASD, according to research published in the November 10, 2009, issue of Neurology®, the medical journal of the American Academy of Neurology. The study, conducted by researchers at the Kennedy Krieger Institute, compared handwriting samples, motor skills, and visuospatial abilities of children with ASD to typically developing children. The researchers found that overall, the handwriting of children with ASD was worse than typically developing children. Specifically, children with ASD had trouble with forming letters, however in other categories, such as size, alignment, and spacing, their handwriting was comparable to typically developing children. These findings build on previous studies examining motor skills and ASD conducted in 2009 by Kennedy Krieger researchers.

Parents of children with ASD are often the first ones to observe their child’s poor handwriting quality. This study identifies fine motor control as a root source of the problem and demonstrates that children with ASD may not experience difficulties across all domains, just forming letters. By identifying handwriting as a legitimate impairment, parents, teachers and therapists will now be able to pursue techniques that will improve children’s handwriting.

“The ability to keep up in classes and convey ideas through handwriting is fundamental to life,” said Christina Fuentes, lead study author and researcher at the Kennedy Krieger Institute. “Knowing the causes of impairment allows us to strategically identify techniques that will help children with ASD improve their handwriting. Our study suggests that teaching children how to form letters, in combination with general training of fine motor control through techniques that include stabilizing the arm and the use of proper writing utensils, may be the best direction for improving handwriting performance.”

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About the studyResearchers administered a total of three tests to 14 children with ASD and 14 typically developing children. The handwriting samples were scored on legibility, form, alignment, size and spacing. The children’s motor skills were then assessed using the Revised Physical and Neurological Examination for Subtle Sign (PANESS). The PANESS consisted of multiple categories such as gait tasks (heel walking), balance tasks (hopping on one foot) and timed movements (repetitive and patterned movements). Lastly, the children’s visuospatial skills were assessed using the Block Design test in which they were timed to reconstruct large designs by properly assembling a set of blocks.

With no significant difference between the typically developing children and children with ASD groups in age, perceptual reasoning IQ, and the Block Design scores, a significant difference was found for performance on the PANESS, with the typically developing children performing better. Researchers found children with ASD’s total handwriting scores were lower than typically developing children due to the quality of their letter formation. Researchers also found that motor ability, specifically for timed movements, was a strong predictor of handwriting performance in children with ASD as opposed to age, intelligence, and visuospatial abilities.

“Identifying this fine motor deficiency in handwriting provides important insight about ASD,” said Dr. Amy Bastian, corresponding study author and Director of the Motion Analysis Laboratory at the Kennedy Krieger Institute. “It provides another example of motor skill problems that may give us cues for other deficits with socialization and communication. Furthermore, occupational therapists and teachers can now take the information from this study and apply it to the students they see on a daily basis.”

This study was sponsored by Autism Speaks and the National Institutes of Health.

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About AutismAutism spectrum disorders (ASD) is the nation’s fastest growing developmental disorder, with current incidence rates estimated at 1 in 100 children. This year more children will be diagnosed with autism than AIDS, diabetes and cancer combined, yet profound gaps remain in our understanding of both the causes and cures of the disorder. Continued research and education about developmental disruptions in individuals with ASD is crucial, as early detection and intervention can lead to improved outcomes in individuals with ASD.

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 13,000 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.

Bullying children with autism

Photo by Quin Stevenson

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BINGHAMTON, NY – Children with autism spectrum disorder (ASD) are more likely to experience bullying than children without ASD and this bullying gets worse with age, according to new research from Binghamton University, State University of New York.

Hannah Morton, a graduate student in the clinical psychology PhD program at Binghamton University, aimed to conceptualize bullying in children with ASD in order to specifically identify different bullying and behavior types. Her research also emphasizes the need to establish better definitions of bullying behaviors.

“This research is important because it contributes to our understanding of how bullying is nuanced,” said Morton. “This variability means it is crucial to establish a definition for bullying and have standard assessments to know when and what types of bullying are occurring.”

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Morton, along with Binghamton psychologists Jennifer Gillis, Richard Mattson and Raymond Romanczyk, focused this study on teachers and parents of children with ASD, and community members without an ASD child. Participants took a survey containing 80 scenarios of interactions between two school-aged children. The scenarios varied from children ages four to fifteen. Sixty-four of these scenarios contained a type of bullying behavior (i.e. physical, verbal, interpersonal and cyber). The participants were randomly presented with 16 scenarios, and were asked to rate the severity of the interaction between the two children, as well as indicate which types of bullying were present.

Results showed that a child’s increased age predicted higher bullying severity ratings. The findings also showed that bullying among older children with ASD is viewed as especially problematic by their parents, and that perceived bullying severity differed according to the type of bullying behavior (i.e., physical, verbal, interpersonal, and cyber). 

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“This paper emphasizes that bullying is a really broad construct,” said Morton. “What any two people might be referring to when they use the term ‘bullying’—regardless if they are parents, teachers, researchers, etc.— likely differs, and perhaps in subtle ways.”

Morton plans to further her research on this topic by focusing specifically on the bullying behaviors that children with ASD experience compared to children without ASD.

This research was conducted through Binghamton University’s Institute for Child Development, which offers early intervention services, speech services and more to children and families in the Binghamton region. 

The paper, “Conceptualizing bullying in children with autism spectrum disorder: Using a mixed model to differentiate behavior types and identify predictors,” was published in Autism.

Parents Left in the Cold When It Comes to Kids with Autism

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First-line health professionals must vastly improve their communication and engagement with parents if they are to help address the growing prevalence of autism among children, say researchers from the University of South Australia.

Undertaking a meta-synthesis of 22 international studies, researchers consolidated the voices of 1178 parents advocating for their children with autism, finding that parents feel ignored and dismissed by medical practitioners as they navigate initial concerns for their child, further investigations, and finally, a formal diagnosis of autism.

Researchers say that medical practitioners need to adopt a family-focused approach to ensure that parents’ concerns, perspectives and observations are taken seriously so that their child has appropriate and timely access to early intervention services.

Autism spectrum disorder (ASD) is a persistent developmental disorder characterised by social difficulties, restricted or repetitive patterns of behaviour, and impaired communication skills. The symptoms can range from mild to severe, with early signs often evident from early childhood.

Autism is one of the most prevalent developmental conditions among children, with one in 70 people in Australia on the spectrum, an estimated 40 per cent increase over the past four years. Internationally, statistics are higher with one in 59 children on the spectrum.

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UniSA lead researcher, Dr Kobie Boshoff, says the parent advocacy role is critical and must be taken more seriously by medical practitioners.

“Parents are natural advocates for their child, making them an invaluable source of information when it comes to complex diagnoses for invisible disabilities like autism,” Dr Boshoff says.

“Yet parents are increasingly finding the diagnosis process overly stressful and complicated.

“In this study, parents commonly reported their concerns for their child were not being heard or taken seriously by medical professionals. They said they felt confused, stressed and frustrated at the lack of support and understanding.

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“They also reported lengthy delays in receiving a diagnosis for their child, as well as a variety of unsatisfactory explanations as alternatives to autism. As access to early intervention services is essential for improving the development outcomes of children with autism, this too is unacceptable.”

Dr Boshoff says first-line medical professionals and service providers must recognise both the role of parents as advocates for their child, and the importance of the parent-practitioner role, which can significantly impact future relationships with other professionals.

She says to build trust medical practitioners must reassess the way they talk and engage with parents.

“First line health professionals and diagnostic services must ensure emotional support is provided to parents throughout the diagnosis process, engaging parents as partners and taking their concerns seriously,” Dr Boshoff says.

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“Autism spectrum disorder is a lifelong developmental condition. A positive experience in the early stages of diagnosis can deliver better relationships with future professionals, and most importantly, secure better outcomes for the children.”

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Media: Annabel Mansfield: office +61 8 8302 0351 | mobile: +61 417 717 504 email: Annabel.Mansfield@unisa.edu.au Lead Researcher: Dr Kobie Boshoff office: +61 8 830 21089 | kobie.boshoff@unisa.edu.au

NOTES TO EDITORS:

Dr Kobie Boshoff will also be presenting this topic at the Healthy Development Adelaide event ‘Research and Developments in Autism: A SA Perspective.’ On Wednesday 30 October 2019, rom 5:30pm – 8:00pm. This is a free event open to everyone.