Research by Topic: Mutations

Podcast: Where the wild new genetic hot spots are

Published May 7, 2018

On this week’s podcast, three genetics papers featuring three ASF fellows! All three deal with using whole genome sequencing (WGS) to study non-coding regulatory regions that may be associated with autism. These regions of DNA do not code for proteins but regulate the regions that do. Mutations in the non-coding regulatory regions that regulate the […]

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Autism and Epilepsy Cases Share Mutations

Published October 15, 2013 in Simons Foundation Autism Research Institute

About one-third of people with autism suffer from epilepsy. This overlap suggests that the two disorders may have a common origin a theory borne out by examples of shared genetics. Mutations in GABRB3, a brain receptor linked to autism, are prevalent in severe childhood epilepsy, according to a study published in Nature. The study also found that many of the spontaneous mutations found in children with epilepsy overlap with those linked to autism and fragile X syndrome.

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Autisms Unexpected Link to Cancer Gene

Published August 11, 2013 in The New York Times

Researchers have recently discovered that two seemingly unrelated conditions, autism and cancer, share an unexpected connection. Some people with autism have specific mutated cancer or tumor genes that scientists believe caused their autism. While this does not apply to all people with autism, just the ones with the mutated gene, it is a very illuminating discovery in the field.

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Studies Show Key Steps of How Mutations to the MeCP2 Gene Cause Rett Syndrome

Published June 16, 2013 in Nature Neuroscience

Two collaborative papers reveal the key steps of how mutations to the MeCP2 gene cause Rett Syndrome by impairing the interaction between MeCP2 and the NCoR/SMRT co-repressor.

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Fragile X Mutation May Produce Toxic Protein Clumps That Cause FXTAS

Published May 8, 2013 in Neuron

University of Michigan study finds that a mild form of the fragile X mutation produces protein clumps that may trigger fragile X-associated tremor/ataxia.

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Global Increases in Both Common and Rare Copy Number Load Associated with Autism

Published March 27, 2013 in Human Molecular Genetics

Penn State researchers link autism to increased genetic change in “hotspots”, regions of the genome that are highly susceptible to mutation.

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Mother’s Drive Helps Research on Rare Autism-linked Mutation

Published March 14, 2013 in SFARI

A mother with two sons with autism helps advance research on neuroligin-4 mutations.

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Published February 21, 2013 in SFARI

SFARI Gene is an integrated resource for the autism research community. It is a publicly available, curated, web-based, searchable database for autism research. This resource is built on information extracted from the studies on molecular genetics and biology of Autism Spectrum Disorders (ASD). The genetic information includes data from linkage and association studies, cytogenetic abnormalities, and specific mutations associated with ASD.

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Rectifying Neuroligin Synthesis Reverses ASD Symptoms in Mice

Published November 21, 2012 in Nature

Abnormally high production of neuroligins, proteins involved in synapse formation, resulted in ASD symptoms in mice. Researchers reversed ASD symptoms by reducing neuroligin synthesis.

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Multiplex Targeted Sequencing Identifies Recurrently Mutated Genes in Autism Spectrum Disorders

Published November 15, 2012 in Science

De novo mutations in six genes may contribute to 1% of simplex ASD cases.

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Common Genetic Variants, Acting Additively, Are a Major Source of Risk for Autism

Published October 15, 2012 in Molecular Autism

Study finds that together, a large number of inherited, common genetic variations of very small effect can increase risk for autism. Suggests risk of inherited ASD is approximately 40% in simplex families and 60% in multiplex families.

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Progress in Identifying the Genetic Roots of Autism

Published September 25, 2012 in Wall Street Journal

Genetic tests are beginning to shed light on the causes of some autism spectrum disorders.

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Fathers Age Is Linked to Risk of Autism and Schizophrenia

Published August 22, 2012 in Nature

Older men are more likely than young ones to father a child who develops autism or schizophrenia, because of random mutations that become more numerous with advancing paternal age, scientists reported on Wednesday, in the first study to quantify the effect as it builds each year. The age of mothers had no bearing on the risk for these disorders, the study found. Full article is here –

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De Novo Mutations in Human Genetic Disease

Published July 18, 2012 in Nature Reviews: Genetics

The influence of genetic mutations on the burden of any genetic disease can usefully be determined using family-based whole-genome or whole-exome sequencing approaches.

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Genetic and Functional Analyses of SHANK2 Mutations Suggest A Multiple Hit Model of Autism Spectrum Disorders

Published February 1, 2012 in PLOS Genetics

“Autism spectrum disorders (ASD) are a heterogeneous group of neurodevelopmental disorders with a complex inheritance pattern. While many rare variants in synaptic proteins have been identified in patients with ASD, little is known about their effects at the synapse and their interactions with other genetic variations. Here, following the discovery of two de novo SHANK2 deletions by the Autism Genome Project, we identified a novel 421 kb de novo SHANK2 deletion in a patient with autism. We then sequenced SHANK2 in 455 patients with ASD and 431 controls and integrated these results with those reported by Berkel et al. 2010 (n?=?396 patients and n?=?659 controls). We observed a significant enrichment of variants affecting conserved amino acids in 29 of 851 (3.4%) patients and in 16 of 1,090 (1.5%) controls (P?=?0.004, OR?=?2.37, 95% CI?=?1.23-4.70). In neuronal cell cultures, the variants identified in patients were associated with a reduced synaptic density at dendrites compared to the variants only detected in controls (P?=?0.0013). Interestingly, the three patients with de novo SHANK2 deletions also carried inherited CNVs at 15q11-q13 previously associated with neuropsychiatric disorders. In two cases, the nicotinic receptor CHRNA7 was duplicated and in one case the synaptic translation repressor CYFIP1 was deleted. These results strengthen the role of synaptic gene dysfunction in ASD but also highlight the presence of putative modifier genes, which is in keeping with the “multiple hit model” for ASD. A better knowledge of these genetic interactions will be necessary to understand the complex inheritance pattern of ASD.”

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