scholarly journals Drosophila functional screening of de novo variants in autism uncovers deleterious variants and facilitates discovery of rare neurodevelopmental diseases

2021 ◽  
Author(s):  
Paul C Marcogliese ◽  
Samantha L Deal ◽  
Jonathan Andrews ◽  
J Michael Harnish ◽  
V Hemanjani Bhavana ◽  
...  
Keyword(s):  
Autism Spectrum Disorders ◽  
Candidate Genes ◽  
De Novo ◽  
Functional Characterization ◽  
Gene Discovery ◽  
Autism Spectrum ◽  
Functional Screening ◽  
Simons Simplex Collection ◽  
Spectrum Disorders

Abstract:Individuals with autism spectrum disorders (ASD) exhibit an increased burden of de novo variants in a broadening range of genes. We functionally tested the effects of ASD missense variants using Drosophila through ‘humanization’ rescue and overexpression-based strategies. We studied 79 ASD variants in 74 genes identified in the Simons Simplex Collection and found 38% of them caused functional alterations. Moreover, we identified GLRA2 as the cause of a spectrum of neurodevelopmental phenotypes beyond ASD in eight previously undiagnosed subjects. Functional characterization of variants in ASD candidate genes point to conserved neurobiological mechanisms and facilitates gene discovery for rare neurodevelopmental diseases.

scholarly journals CACNA1D De Novo Mutations in Autism Spectrum Disorders Activate Cav1.3 L-Type Calcium Channels

2015 ◽  
Vol 77 (9) ◽  
pp. 816-822 ◽  
Author(s):  
Alexandra Pinggera ◽  
Andreas Lieb ◽  
Bruno Benedetti ◽  
Michaela Lampert ◽  
Stefania Monteleone ◽  
...  
Keyword(s):  
Autism Spectrum Disorders ◽  
Calcium Channels ◽  
De Novo ◽  
Autism Spectrum ◽  
De Novo Mutations ◽  
Spectrum Disorders

scholarly journals The need for a comprehensive molecular characterization of autism spectrum disorders

2013 ◽  
Vol 17 (04) ◽  
pp. 651-673 ◽  
Author(s):  
Jantine A. C. Broek ◽  
Eva Brombacher ◽  
Viktoria Stelzhammer ◽  
Paul C. Guest ◽  
Hassan Rahmoune ◽  
...  
Keyword(s):  
Autism Spectrum Disorders ◽  
Molecular Characterization ◽  
Autism Spectrum ◽  
Spectrum Disorders

scholarly journals Patterns and rates of exonic de novo mutations in autism spectrum disorders

Nature ◽  
2012 ◽  
Vol 485 (7397) ◽  
pp. 242-245 ◽  
Author(s):  
Benjamin M. Neale ◽  
Yan Kou ◽  
Li Liu ◽  
Avi Ma’ayan ◽  
Kaitlin E. Samocha ◽  
...  
Keyword(s):  
Autism Spectrum Disorders ◽  
De Novo ◽  
Autism Spectrum ◽  
De Novo Mutations ◽  
Spectrum Disorders

scholarly journals Progress Towards Simple and Direct Detection of Adenylosuccinate Lyase Deficiency in Human Urine

2011 ◽  
Vol 64 (11) ◽  
pp. 1470 ◽  
Author(s):  
Soojin Lim ◽  
Mark Lowry ◽  
Robert M. Strongin
Keyword(s):  
Autism Spectrum Disorders ◽  
Human Urine ◽  
Boronic Acid ◽  
De Novo ◽  
Direct Detection ◽  
Autism Spectrum ◽  
Purine Synthesis ◽  
Adenylosuccinate Lyase ◽  
Adenylosuccinate Lyase Deficiency ◽  
Spectrum Disorders

A rhodamine based boronic acid linearly responds to increasing 5-aminoimidazole-4-carboxamide riboside (AICAr) concentrations in human urine. This method is thus an advance in detecting adenylosuccinate lyase (ADSL) deficiency as AICAr is a model riboside for the ADSL substrates succinyladenosine (S-Ado) and succinylaminoimidazolecarboxamide riboside (SAICAr). ADSL deficiency is a rare but devastating disease of de novo purine synthesis in infants. Its diagnosis is also significant as it is one of the autism spectrum disorders.

scholarly journals Analysis of the chromosome X exome in patients with autism spectrum disorders identified novel candidate genes, including TMLHE

2012 ◽  
Vol 2 (10) ◽  
pp. e179-e179 ◽  
Author(s):  
C Nava ◽  
F Lamari ◽  
D Héron ◽  
C Mignot ◽  
A Rastetter ◽  
...  
Keyword(s):  
Autism Spectrum Disorders ◽  
Candidate Genes ◽  
Autism Spectrum ◽  
Chromosome X ◽  
Spectrum Disorders

An Overview of the Genetics of Autism Spectrum Disorders

2013 ◽  
Author(s):  
Joseph D. Buxbaum
Keyword(s):  
Autism Spectrum Disorders ◽  
Gene Discovery ◽  
Autism Spectrum ◽  
Good Evidence ◽  
Not Otherwise Specified ◽  
Second Generation Sequencing ◽  
Spectrum Disorders ◽  
Clinical Measures ◽  
Functional Analyses ◽  
Generation Sequencing

There is very good evidence for a strong genetic component to the autism spectrum disorders (ASDs), which include autistic disorder, Asperger syndrome, pervasive developmental disorder not otherwise specified, and Rett syndrome. At the same time, identifying the loci contributing to ASD risk has proven difficult because of extreme heterogeneity. However, in spite of these difficulties, many ASD loci have been identified and, even using current clinical measures, an etiological diagnosis can be given in upward of 20% of cases. With the introduction of “second-generation” sequencing, gene discovery in ASDs will accelerate. As genes are being discovered, functional analyses are leading to potential novel therapeutics, and there is great optimism for more effective treatments in ASDs arising from gene discovery. In the current review, some of the important findings in ASD genetics will be outlined, as will the next steps in ASD genetics.

scholarly journals High-throughput sequencing of autism spectrum disorders comes of age

2013 ◽  
Vol 95 (4) ◽  
pp. 121-129 ◽  
Author(s):  
MINGBANG WANG ◽  
XIAOMEI FAN ◽  
TAO WANG ◽  
JINYU WU
Keyword(s):  
Autism Spectrum Disorders ◽  
High Throughput ◽  
High Throughput Sequencing ◽  
De Novo ◽  
Autism Spectrum ◽  
Disease Gene Discovery ◽  
The Usa ◽  
High Heritability ◽  
Spectrum Disorders ◽  
Promising Perspective

SummaryAutism spectrum disorders (ASDs) are lifelong neurodevelopmental disabilities that affect 1 in 88 children in the USA. Despite the high heritability, the genetic basis for a majority of the ASDs remains elusive. The considerable clinical and genetic heterogeneity pose a significant challenge technically. State-of-the-art high-throughput sequencing (HTS), which makes the analyses of any specific single/multiple genes or whole exomes feasible, has shown a promising perspective in disease gene discovery. To date, numerous genetic studies using HTS have been reported and many rare inherited or de novo mutations have been identified. This review will focus on the progress and prospective of genome studies of ASDs using HTS.

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