Published articles related to dup15q syndrome

October 30, 2019
Behavioral characterization of dup15q syndrome: Toward meaningful endpoints for clinical trials
Charlotte DiStefano, Rujuta B. Wilson, Carly Hyde, Edwin H. Cook, Ronald L. Thibert 

Lawrence T. Reiter, Vanessa Vogel‐Farley, Joerg Hipp, Shafali Jeste

Duplication of 15q11.2‐q13.1 (dup15q syndrome) is one of the most common copy number variations associated with autism spectrum disorders (ASD) and intellectual disability (ID). As with many neurogenetic conditions, accurate behavioral assessment is challenging due to the level of impairment and heterogeneity across individuals. Large‐scale phenotyping studies are necessary to inform future clinical trials in this and similar ID syndromes.

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August 12, 2019
Dup15q Alliance and the Angelman Syndrome Foundation jointly funding research that will build the first 3D structure of UBE3A

The Dup15q Alliance and the Angelman Syndrome Foundation are excited to announce a jointly funded research project that will build the first 3D structure of UBE3A. Gilles Trave, PhD from the European Center of Research and Biology in Illkirch, France will study the interaction between UBE3A and HERC2 proteins to regulate important genes for neurodevelopment and better understand how UBE3A and HERC2 work together. Dr. Trave hopes to gain an understanding of how UBE3A works with HERC2 to impact brain development and will build the first ever 3D structure of UBE3A with and without HERC2. 

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July 30, 2019
State of the Field: Differentiating Intellectual Disability From Autism Spectrum Disorder

Audrey Thurm1*, Cristan Farmer1, Emma Salzman2, Catherine Lord3 and Somer Bishop2

1 Neurodevelopmental and Behavioral Phenotyping Service, Office of the Clinical Director, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, United States, 2 UCSF Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA, United States, 3 Semel Institute of Neuroscience and Human Behavior, David Geffen School of Medicine at UCLA, Los Angeles, CA, United States

The topic of this special issue on secondary versus idiopathic autism allows for discussion of how different groups may come to manifest autism spectrum disorder (ASD) or ASDlike symptoms despite important etiological differences

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July 27, 2019
Long-term safety and efficacy of cannabidiol in children and adults with treatment resistant Lennox-Gastaut syndrome or Dravet syndrome: Expanded access program results

Linda C.Lauxa, E. Martina Bebinb,  Daniel Checkettsc,  Michael Chezd,  Robert Flaminie, Eric D.Marshf, Ian Millerg, Kathryn Nicholh,Yong Parki, Eric Segalj, Laurie Seltzerk, Jerzy P.Szaflarskib, Elizabeth A. Thielel, Arie Weinstockm, on behalf of CBD EAP study group

Since 2014, patients with severe treatment-resistant epilepsies (TREs) have been receiving add-on cannabidiol (CBD) in an ongoing, expanded access program (EAP), which closely reflects clinical practice. We conducted an interim analysis of long-term efficacy and tolerability in patients with Lennox-Gastaut syndrome (LGS) or Dravet syndrome (DS) who received CBD treatment through December 2016.

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July 3, 2019
Mechanisms underlying the EEG biomarker in Dup15q syndrome

Authors: Joel Frohlich1,2,3* , Lawrence T. Reiter4 , Vidya Saravanapandian2 , Charlotte DiStefano2 , Scott Huberty2,5, Carly Hyde2 , Stormy Chamberlain6 , Carrie E. Bearden7 , Peyman Golshani8 , Andrei Irimia9 , Richard W. Olsen10, Joerg F. Hipp1† and Shafali S. Jeste2†

Duplications of 15q11.2-q13.1 (Dup15q syndrome), including the paternally imprinted gene UBE3A and three nonimprinted gamma-aminobutyric acid type-A (GABAA) receptor genes, are highly penetrant for neurodevelopmental disorders such as autism spectrum disorder (ASD). To guide targeted treatments of Dup15q syndrome and other forms of ASD, biomarkers are needed that reflect molecular mechanisms of pathology. We recently described a beta EEG phenotype of Dup15q syndrome, but it remains unknown which specific genes drive this phenotype.

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June 26, 2019
Epigenomic Convergence of Neural-Immune Risk Factors in Neurodevelopmental Disorder Cortex

Authors: A Vogel Ciernia B I Laufer H Hwang K W Dunaway C E Mordaunt R L Coulson D H YasuiJ M LaSalle

Neurodevelopmental disorders (NDDs) affect 7–14% of all children in developed countries and are one of the leading causes of lifelong disability. Epigenetic modifications are poised at the interface between genes and environment and are predicted to reveal insight into NDD etiology. 

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June 19, 2019
SUDEP in the North American SUDEP Registry

Authors: Chloe Verducci, BA, Fizza Hussain, MS, Elizabeth Donner, MD FRCP(C), Brian D. Moseley, MD, Jeffrey Buchhalter, MD, Dale Hesdorffer, PhD, Daniel Friedman, MD, MSc, and Orrin Devinsky, MD

There were 237 definite and probable cases of SUDEP among 530 NASR participants. SUDEP decedents had a median age of 26 (range 1–70) years at death, and 38% were female. In 143 with sufficient information, 40% had generalized and 60% had focal epilepsy. SUDEP affected the full spectrum of epilepsies, from benign epilepsy with centrotemporal spikes (n = 3, 1%) to intractable epileptic encephalopathies (n = 27, 11%). Most (93%) SUDEPs were unwitnessed; 70% occurred during apparent sleep; and 69% of patients were prone. Only 37% of cases of SUDEP took their last dose of antiseizure medications (ASMs). Reported lifetime generalized tonic-clonic seizures (GTCS) were <10 in 33% and 0 in 4%.

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May 29, 2019
SUDEP in patients with epilepsy and nonepileptic seizures

Chloe Verducci, Daniel Friedman, Orrin Devinsky

We report 13 SUDEP cases in the North American SUDEP Registry with both psychogenic nonepileptic seizures (PNES) and epileptic seizures (ES) among a consecutive series of 231 cases (excluding epileptic encephalopathies). On average, cases of PNES + ES died at a younger age (23 ± 11 years) than the ES‐only cohort (30 ± 14 years), and died an average of 3 years after PNES diagnosis. We found no statistically significant confounding cardiac, respiratory, or psychiatric comorbidities and equal rates of anti‐seizure medication adherence, although there was a trend for higher rates of psychiatric disorders in the PNES group. Our findings confirm that patients with comorbid ES and PNES can die from SUDEP and that there may be a high‐risk period after the diagnosis of PNES is made in patients with comorbid ES. Such patients should be closely monitored and provided with coordinated care of both their epilepsy and psychiatric disorder(s).

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May 3, 2019
Behavioral neuroscience of autism

Toru Takumia Kota Tamadaa Fumiyuki Hatanakaa Nobuhiro Nakaia Patrick F. Boltonb

Autism spectrum disorder (ASD) is a neurodevelopmental disorder. Several genetic causes of ASD have been identified and this has enabled researchers to construct mouse models. Mouse behavioral tests reveal impaired social interaction and communication, as well as increased repetitive behavior and behavioral inflexibility in these mice, which correspond to core behavioral deficits observed in individuals with ASD.

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May 1, 2019
Electrophysiological Phenotype in Angelman Syndrome Differs Between Genotypes

Joel Frohlich,  Meghan T.Miller, Lynne  M. Bird, Pilar  Garces, Hannah Purtell, Marius C. Hoener, Benjamin D.Philpot, Michael S.Sidorov, Wen-HannTan, Maria-Clemencia Hernandez, Alexander Rotenberg, Shafali S.Jeste, Michelle Krishnana, Omar Khwajaa Joerg F. Hippa

BACKGROUND:Angelman syndrome (AS) is a severe neurodevelopmental disorder caused by either disruptions ofthe geneUBE3Aor deletion of chromosome 15 at 15q11-q13, which encompassesUBE3Aand several other genes,includingGABRB3,GABRA5,GABRG3, encoding gamma-aminobutyric acid type A receptor subunits (b3,a5,g3).Individuals with deletions are generally more impaired than those with other genotypes, but the underlyingpathophysiology remains largely unknown. Here, we used electroencephalography (EEG) to test the hypothesisthat genes other thanUBE3Alocated on 15q11-q13 cause differences in pathophysiology between AS genotypes

BACKGROUND:Angelman syndrome (AS) is a severe neurodevelopmental disorder caused by either disruptions ofthe geneUBE3Aor deletion of chromosome 15 at 15q11-q13, which encompassesUBE3Aand several other genes,includingGABRB3,GABRA5,GABRG3, encoding gamma-aminobutyric acid type A receptor subunits (b3,a5,g3).Individuals with deletions are generally more impaired than those with other genotypes, but the underlyingpathophysiology remains largely unknown. Here, we used electroencephalography (EEG) to test the hypothesisthat genes other thanUBE3Alocated on 15q11-q13 cause differences in pathophysiology between AS genotypesBACKGROUND:Angelman syndrome (AS) is a severe neurodevelopmental disorder caused by either disruptions ofthe geneUBE3Aor deletion of chromosome 15 at 15q11-q13, which encompassesUBE3Aand several other genes,includingGABRB3,GABRA5,GABRG3, encoding gamma-aminobutyric acid type A receptor subunits (b3,a5,g3).Individuals with deletions are generally more impaired than those with other genotypes, but the underlyingpathophysiology remains largely unknown. Here, we used electroencephalography (EEG) to test the hypothesisthat genes other thanUBE3Alocated on 15q11-q13 cause differences in pathophysiology between AS genotypes

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