Tag Archives: diagnosis of autism

University of California San Francisco study: Dozens of genes associated with autism

29 Oct

The number of children with autism appears to be growing. The Centers for Disease Control and Prevention provides statistics on the number of children with autism in the section Data and Statistics:

Prevalence

  • It is estimated that between 1 in 80 and 1 in 240 with an average of 1 in 110 children in the United States have an ASD. [Read article]

  • ASDs are reported to occur in all racial, ethnic, and socioeconomic groups, yet are on average 4 to 5 times more likely to occur in boys than in girls.  However, we need more information on some less studied populations and regions around the world. [Read article]

  • Studies in Asia, Europe, and North America have identified individuals with an ASD with an approximate prevalence of 0.6% to over 1%. A recent study in South Korea reported a prevalence of 2.6%. [Data table ]

  • Approximately 13% of children have a developmental disability, ranging from mild disabilities such as speech and language impairments to serious developmental disabilities, such as intellectual disabilities, cerebral palsy, and autism.  [Read article] http://www.cdc.gov/ncbddd/autism/data.html

In order for children with autism to reach their full potential there must be early diagnosis and treatment.

Science Daily reported in Dozens of genes associated with autism in new research:

Two major genetic studies of autism, led in part by UC San Francisco scientists and involving more than 50 laboratories worldwide, have newly implicated dozens of genes in the disorder. The research shows that rare mutations in these genes affect communication networks in the brain and compromise fundamental biological mechanisms that govern whether, when, and how genes are activated overall.

The two new studies, published in the advance online edition of Nature on October 29, 2014, tied mutations in more than 100 genes to autism. Sixty of these genes met a “high-confidence” threshold indicating that there is a greater than 90 percent chance that mutations in those genes contribute to autism risk.

The majority of the mutations identified in the new studies are de novo (Latin for “afresh”) mutations, meaning they are not present in unaffected parents’ genomes but arise spontaneously in a single sperm or egg cell just prior to conception of a child.

The genes implicated in the new studies fall into three broad classes: they are involved in the formation and function of synapses, which are sites of nerve-cell communication in the brain; they regulate, via a process called transcription, how the instructions in other genes are relayed to the protein-making machinery in cells; and they affect how DNA is wound up and packed into cells in a structure known as chromatin. Because modifications of chromatin structure are known to lead to changes in how genes are expressed, mutations that alter chromatin, like those that affect transcription, would be expected to affect the activity of many genes.

One of the new Nature studies made use of data from the Simons Simplex Collection (SSC), a permanent repository of DNA samples from nearly 3,000 families created by the Simons Foundation Autism Research Initiative. Each SSC family has one child affected with autism, parents unaffected by the disorder and, in a large proportion, unaffected siblings. The second study was conducted under the auspices of the Autism Sequencing Consortium (ASC), an initiative supported by the National Institute of Mental Health that allows scientists from around the world to collaborate on large genomic studies that couldn’t be done by individual labs.

“Before these studies, only 11 autism genes had been identified with high confidence, and we have now more than quadrupled that number,” said Stephan Sanders, PhD, assistant professor of psychiatry at UCSF, co-first author on the SSC study, and co-author on the ASC study. Based on recent trends, Sanders estimates that gene discovery will continue at a quickening pace, with as many as 1,000 genes ultimately associated with autism risk.

“There has been a lot of concern that 1,000 genes means 1,000 different treatments, but I think the news is much brighter than that,” said Matthew W. State, MD, PhD, chair and Oberndorf Family Distinguished Professor in Psychiatry at UCSF. State was co-leader of the Nature study focusing on the SSC and a senior participant in the study organized by the ASC, of which he is a co-founder. ”There is already strong evidence that these mutations converge on a much smaller number key biological functions. We now need to focus on these points of convergence to begin to develop novel treatments….”                                                                                                                            http://www.sciencedaily.com/releases/2014/10/141029141223.htm

Citation:

Dozens of genes associated with autism in new research

Date:             October 29, 2014

Source:         University of California, San Francisco (UCSF)

Summary:

Two major genetic studies of autism, involving more than 50 laboratories worldwide, have newly implicated dozens of genes in the disorder. The research shows that rare mutations in these genes affect communication networks in the brain and compromise fundamental biological mechanisms that govern whether, when, and how genes are activated overall.

Nature | Article

Synaptic, transcriptional and chromatin genes disrupted in autism

Nature

(2014)

doi:10.1038/nature13772

Received

18 May 2014

Accepted

18 August 2014

Published online

29 October 2014

Abstract

  • Abstract•

The genetic architecture of autism spectrum disorder involves the interplay of common and rare variants and their impact on hundreds of genes. Using exome sequencing, here we show that analysis of rare coding variation in 3,871 autism cases and 9,937 ancestry-matched or parental controls implicates 22 autosomal genes at a false discovery rate (FDR) < 0.05, plus a set of 107 autosomal genes strongly enriched for those likely to affect risk (FDR < 0.30). These 107 genes, which show unusual evolutionary constraint against mutations, incur de novo loss-of-function mutations in over 5% of autistic subjects. Many of the genes implicated encode proteins for synaptic formation, transcriptional regulation and chromatin-remodelling pathways. These include voltage-gated ion channels regulating the propagation of action potentials, pacemaking and excitability–transcription coupling, as well as histone-modifying enzymes and chromatin remodellers—most prominently those that mediate post-translational lysine methylation/demethylation modifications of histones.                                                                                   http://www.nature.com/nature/journal/vaop/ncurrent/full/nature13772.html

Here is the press release from the University of California San Francisco:

Dozens of Genes Associated with Autism in New Research

Functions of Newly Identified Genes Converge on a Few Important Biological Processes

By Pete Farley on October 29, 2014 | Email | Print

Two major genetic studies of autism, led in part by UC San Francisco scientists and involving more than 50 laboratories worldwide, have newly implicated dozens of genes in the disorder. The research shows that rare mutations in these genes affect communication networks in the brain and compromise fundamental biological mechanisms that govern whether, when, and how genes are activated overall.

The two new studies, published in the advance online edition of Nature on October 29, 2014, tied mutations in more than 100 genes to autism. Sixty of these genes met a “high-confidence” threshold indicating that there is a greater than 90 percent chance that mutations in those genes contribute to autism risk.

The majority of the mutations identified in the new studies are de novo (Latin for “afresh”) mutations, meaning they are not present in unaffected parents’ genomes but arise spontaneously in a single sperm or egg cell just prior to conception of a child.

The genes implicated in the new studies fall into three broad classes: they are involved in the formation and function of synapses, which are sites of nerve-cell communication in the brain; they regulate, via a process called transcription, how the instructions in other genes are relayed to the protein-making machinery in cells; and they affect how DNA is wound up and packed into cells in a structure known as chromatin. Because modifications of chromatin structure are known to lead to changes in how genes are expressed, mutations that alter chromatin, like those that affect transcription, would be expected to affect the activity of many genes.

One of the new Nature studies made use of data from the Simons Simplex Collection (SSC), a permanent repository of DNA samples from nearly 3,000 families created by the Simons Foundation Autism Research Initiative. Each SSC family has one child affected with autism, parents unaffected by the disorder and, in a large proportion, unaffected siblings. The second study was conducted under the auspices of the Autism Sequencing Consortium (ASC), an initiative supported by the National Institute of Mental Health that allows scientists from around the world to collaborate on large genomic studies that couldn’t be done by individual labs.

“Before these studies, only 11 autism genes had been identified with high confidence, and we have now more than quadrupled that number,” said Stephan Sanders, PhD, assistant professor of psychiatry at UCSF, co-first author on the SSC study, and co-author on the ASC study. Based on recent trends, Sanders estimates that gene discovery will continue at a quickening pace, with as many as 1,000 genes ultimately associated with autism risk.

“There has been a lot of concern that 1,000 genes means 1,000 different treatments, but I think the news is much brighter than that,” said Matthew W. State, MD, PhD, chair and Oberndorf Family Distinguished Professor in Psychiatry at UCSF. State was co-leader of the Nature study focusing on the SSC and a senior participant in the study organized by the ASC, of which he is a co-founder. ”There is already strong evidence that these mutations converge on a much smaller number key biological functions. We now need to focus on these points of convergence to begin to develop novel treatments.

Autism, which is marked by deficits in social interaction and language development, as well as by repetitive behaviors and restricted interests, is known to have a strong genetic component. But until a few years ago, genomic research had failed to decisively associate individual genes with the disorder.

The two new studies highlight the factors that have radically changed that picture, State said. One is the advent of next-generation sequencing (NGS), which allows researchers to read each of the “letters” in the DNA code at unprecedented speed. Another is the establishment of the SSC; a 2007 study had suggested that de novo mutations would play a significant role in autism risk, and the SSC was specifically designed to help test that idea by allowing for close comparisons between children with autism and their unaffected parents and siblings. Lastly, collaborative initiatives such as the ASC are enabling teams of researchers around the world to work closely together, pooling their resources to create large datasets with sufficient statistical power to draw valid conclusions.

The large research teams behind each of the two new studies used a form of NGS known as “whole-exome” sequencing, a letter-by-letter analysis of just the portion of the genome that encodes proteins.

In November 2013, a study led by A. Jeremy Willsey, a graduate student in State’s lab, showed that the functional roles of the nine high-confidence autism risk genes that had then been discovered all converged on a single cell type in a particular place in the brain at a particular time during fetal development. Willsey is a co-author on both of the new Nature studies, which State believes will further accelerate our understanding of how the myriad of genes involved in autism affect basic biological pathways in the brain.

“These genes carry really large effects,” State said. “That we now have a bounty of dozens of genes, and a clear path forward to find perhaps hundreds more, provides an incredible foundation for understanding the biology of autism and finding new treatments.”

UCSF is the nation’s leading university exclusively focused on health. Now celebrating the 150th anniversary of its founding as a medical college, UCSF is dedicated to transforming health worldwide through advanced biomedical research, graduate-level education in the life sciences and health professions, and excellence in patient care. It includes top-ranked graduate schools of dentistry, medicine, nursing and pharmacy; a graduate division with world-renowned programs in the biological sciences, a preeminent biomedical research enterprise and top-tier hospitals, UCSF Medical Center and UCSF Benioff Children’s Hospitals.

It is imperative that ALL women receive prenatal care particularly poor and those women at risk of difficult pregnancies. Early diagnosis of autism gives the child the best chance of achieving their potential.

Related:

Autism and children of color                                                                                                                                                                                       https://drwilda.com/tag/children-of-color-with-autism/

Archives of Pediatrics and Adolescent Medicine study: Kids with autism more likely to be bullied                                     https://drwilda.com/2012/09/06/archives-of-pediatrics-and-adolescent-medicine-study-kids-with-autism-more-likely-to-be-bullied/

Father’s age may be linked to Autism and Schizophrenia                                                                                                     https://drwilda.com/2012/08/26/fathers-age-may-be-linked-to-autism-and-schizophrenia/

Chelation treatment for autism might be harmful                                                                                                                                                  https://drwilda.com/2012/12/02/chelation-treatment-for-autism-might-be-harmful/

Journal of American Medical Association study: Folic acid may reduce autism risk                                               https://drwilda.com/tag/folic-acid-in-pregnancy-may-lower-autism-risk/

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University of Connecticut study: Some children with autism may be ‘cured’ with intense early therapy

19 Jan

In Autism and children of color, moi said:

The number of children with autism appears to be growing. The Centers for Disease Control and Prevention provides statistics on the number of children with autism in the section Data and Statistics:

Prevalence

  • It is estimated that between 1 in 80 and 1 in 240 with an average of 1 in 110 children in the United States have an ASD. [Read article

  • ASDs are reported to occur in all racial, ethnic, and socioeconomic groups, yet are on average 4 to 5 times more likely to occur in boys than in girls.  However, we need more information on some less studied populations and regions around the world. [Read article]

  • Studies in Asia, Europe, and North America have identified individuals with an ASD with an approximate prevalence of 0.6% to over 1%. A recent study in South Korea reported a prevalence of 2.6%. [Data table Adobe PDF file]

  • Approximately 13% of children have a developmental disability, ranging from mild disabilities such as speech and language impairments to serious developmental disabilities, such as intellectual disabilities, cerebral palsy, and autism.  [Read articleExternal Web Site Icon]

Learn more about prevalence of ASDs »

Learn more about the ADDM Project »

Learn more about the MADDSP Project »

On this Page

http://www.cdc.gov/ncbddd/autism/data.html

In order for children with autism to reach their full potential there must be early diagnosis and treatment. https://drwilda.com/2012/03/27/autism-and-children-of-color/

Autism Speaks reports about a University of Connecticut study in the post, Study Confirms “Optimal Outcomes”:

Some children diagnosed with autism in early childhood reach “optimal outcomes” with levels of function similar to their typical peers. The findings appear today in the Journal of Child Psychology and Psychiatry.

“Although the diagnosis of autism is not usually lost over time, the findings suggest that there is a very wide range of possible outcomes,” says Thomas Insel, M.D., director of the National Institutes of Mental Health (NIMH). “For an individual child, the outcome may be knowable only with time and after some years of intervention.”

This week’s report is the first in a series of autism studies on optimal outcomes, sponsored by the NIMH. They follow up on earlier reports that a small group of children appear to “lose” their autism diagnosis over time. Some experts have questioned the accuracy of these children’s initial diagnoses. Others argued that simply being able to function in a mainstream classroom doesn’t mean that these children don’t quietly struggle with autism-related disabilities. http://www.autismspeaks.org/science/science-news/study-confirms-%E2%80%9Coptimal-outcomes%E2%80%9D

Here is the University of Connecticut press release:

Researchers Find Possibility of Change in Children Previously Diagnosed with Autism

January 17, 2013

UConn psychology professor Deborah Fein is the lead author of an article just published in the Journal of Child Psychology and Psychiatry which indicates that some children who are accurately diagnosed with autism in early childhood may lose the symptoms as they grow older.

The article, “Optimal Outcome in Individuals with a History of Autism,” appears in the February 2013 issue of the publication. Co-authors include Professor Marianne Barton, director of clinical training and director of the Psychological Services Clinic in UConn’s Department of Psychology.

Autism Spectrum Disorder and autism are both general terms for a group of complex disorders of brain development. These disorders are characterized, in varying degrees, by difficulties in social interaction and verbal and nonverbal communication, and repetitive behaviors. Statistics from the U.S. Centers for Disease Control and Prevention identify around 1 in 88 American children as being on the autism spectrum.

Fein, UConn Board of Trustees Distinguished Professor of Psychology, has been a leader in autism research since she first worked with children with the disability in the early 1970s. She says the findings in the current study are important, but like much research, raise other questions that are as yet unanswered.

We want to find out what percentage of children are capable of a favorable outcome, what type of behavioral intervention is necessary, what is it in a child’s brain that allows change to take place,” she says. “One thing we do know is that in virtually every case of a child who loses the symptoms of this disorder, the outcome is due to years of unwavering dedication and hard work by parents, teachers, and the children themselves.”

Study methodology

The study, supported by the National Institutes of Health, consisted of carefully documenting a prior diagnosis of autism in a small group of school-age children and young adults with no current symptoms of the disorder who were functioning on a par with their mainstream peers. These 34 children were considered the Optimal Outcome group. This group was then compared with two other cohorts consisting of 44 children with high-functioning autism and 34 children with typical development.

This report is the first in a series that will probe more deeply into the nature of the change in the status of the Optimal Outcome children. Having at one time been diagnosed with Autism Spectrum Disorder, these young people now appear equal to typically developing peers. The study team is continuing to analyze data on changes in brain function in these children, and attempting to determine whether they have subtle residual social deficits.

Also under review is the type of interventions these children received, and to what extent that intervention is predictive of a successful transition.

Although the diagnosis of autism is not usually lost over time, the findings suggest that there is a very wide range of possible outcomes,” says Dr. Thomas R. Insel, director of the National Institute of Mental Health. “For an individual child, the outcome may be knowable only with time and after some years of intervention. Subsequent reports from this study should tell us more about the nature of autism, and the role of therapy and other factors in the long-term outcomes for these children.”

Prior studies have examined the possibility of a loss of diagnosis, but questions remained regarding the accuracy of the initial diagnosis and whether children who ultimately appeared similar to their mainstream peers initially had a relatively mild form of autism.

In Fein’s study, early diagnostic reports by clinicians with expertise in autism diagnosis were reviewed by the investigators. As a second step to ensure accuracy, a diagnostic expert without knowledge of the child’s current status reviewed reports in which the earlier diagnosis had been deleted.

The results suggested that children in the Optimal Outcome group had milder social deficits than the high functioning autism group in early childhood, but had other symptoms, related to communication and repetitive behavior, that were as severe as the latter group.

In addition, to be included in the Optimal Outcome group, children had to be in regular education classrooms with no special education services aimed at autism, and not show any signs of problems with language, face recognition, communication, and social interaction.

Ongoing research

While the current study cannot provide information on what percentage of children diagnosed with Autism Spectrum Disorder might eventually lose the symptoms, investigators have collected a variety of information on the children, including structural and functional brain imaging data, psychiatric outcomes, and information on the therapies the children received.

Analysis of that data, which will be reported in subsequent papers, may shed light on questions such as whether the changes in diagnosis resulted from a normalizing of brain function, or if these children’s brains were able to compensate for autism-related difficulties.

According to Fein, “All children with Autism Spectrum Disorder are capable of making progress with intensive therapy, but with our current state of knowledge, most do not achieve the kind of optimal outcome that we are studying. Our hope is that further research will help us better understand the mechanisms of change so that each child can have the best possible life.”

Citation:

Optimal outcome in individuals with a history of autism

  1. Deborah Fein1,6,
  2. Marianne Barton1,
  3. Inge-Marie Eigsti1,
  4. Elizabeth Kelley2,
  5. Letitia Naigles1,
  6. Robert T. Schultz3,
  7. Michael Stevens4,
  8. Molly Helt1,
  9. Alyssa Orinstein1,
  10. Michael Rosenthal5,
  11. Eva Troyb1,
  12. Katherine Tyson1

Article first published online: 16 JAN 2013

DOI: 10.1111/jcpp.12037

© 2013 The Authors. Journal of Child Psychology and Psychiatry © 2013 Association for Child and Adolescent Mental Health.

Journal of Child Psychology and Psychiatry

Volume 54, Issue 2, pages 195–205, February 2013

http://onlinelibrary.wiley.com/doi/10.1111/jcpp.12037/full

The National Institute of Neurological Disorders and Stroke has an autism fact sheet

A diagnosis of autism can be heartbreaking for families and many cling to any shred of hope that there might be a treatment or a cure. Families have to be careful about the treatments and therapies they seek for their children.

Related:

Father’s age may be linked to Autism and Schizophrenia https://drwilda.com/2012/08/26/fathers-age-may-be-linked-to-autism-and-schizophrenia/

Autism and children of color                                                https://drwilda.com/tag/autism-not-diagnosed-as-early-in-minority-children/

Archives of Pediatrics and Adolescent Medicine study: Kids with autism more likely to be bullied                                   https://drwilda.com/2012/09/06/archives-of-pediatrics-and-adolescent-medicine-study-kids-with-autism-more-likely-to-be-bullied/

Chelation treatment for autism might be harmful               https://drwilda.com/2012/12/02/chelation-treatment-for-autism-might-be-harmful/

Where information leads to Hope. ©                 Dr. Wilda.com

Dr. Wilda says this about that ©

Blogs by Dr. Wilda:

COMMENTS FROM AN OLD FART©                           http://drwildaoldfart.wordpress.com/

Dr. Wilda Reviews ©                                                 http://drwildareviews.wordpress.com/

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