Person:
D'Angelo, Eugene

Profile Picture

Email Address

AA Acceptance Date

Birth Date

Research Projects

Organizational Units

Job Title

Last Name

D'Angelo

First Name

Eugene

Name

D'Angelo, Eugene

Filters

2016 - 20182

Settings

Author's Publications: search.filters.isAuthorOfPublication.5f1de7ba-a338-4a30-97db-8d3c6d1502bb

Search Results

Now showing 1 - 2 of 2
  • Thumbnail Image
    Publication
    De novo ATP1A3 and compound heterozygous NLRP3 mutations in a child with autism spectrum disorder, episodic fatigue and somnolence, and muckle-wells syndrome
    (Elsevier, 2018) Torres, Alcy; Brownstein, Catherine; Tembulkar, Sahil K.; Graber, Kelsey; Genetti, Casie; Kleiman, Robin J.; Sweadner, Kathleen; Mavros, Chrystal; Liu, Kevin X.; Smedemark-Margulies, Niklas; Maski, Kiran; Yang, Edward; Agrawal, Pankaj; Shi, Jiahai; Beggs, Alan; D'Angelo, Eugene; Lincoln, Sarah Hope; Carroll, Devon; Dedeoglu, Fatma; Gahl, William A.; Biggs, Catherine M.; Swoboda, Kathryn; Berry, Gerard; Gonzalez-Heydrich, Joseph
    Complex phenotypes may represent novel syndromes that are the composite interaction of several genetic and environmental factors. We describe an 9-year old male with high functioning autism spectrum disorder and Muckle-Wells syndrome who at age 5 years of age manifested perseverations that interfered with his functioning at home and at school. After age 6, he developed intermittent episodes of fatigue and somnolence lasting from hours to weeks that evolved over the course of months to more chronic hypersomnia. Whole exome sequencing showed three mutations in genes potentially involved in his clinical phenotype. The patient has a predicted pathogenic de novo heterozygous p.Ala681Thr mutation in the ATP1A3 gene (chr19:42480621C>T, GRCh37/hg19). Mutations in this gene are known to cause Alternating Hemiplegia of Childhood, Rapid Onset Dystonia Parkinsonism, and CAPOS syndrome, sometimes accompanied by autistic features. The patient also has compound heterozygosity for p.Arg490Lys/p.Val200Met mutations in the NLRP3 gene (chr1:247588214G>A and chr1:247587343G>A, respectively). NLRP3 mutations are associated in an autosomal dominant manner with clinically overlapping auto-inflammatory conditions including Muckle-Wells syndrome. The p.Arg490Lys is a known pathogenic mutation inherited from the patient's father. The p.Val200Met mutation, inherited from his mother, is a variant of unknown significance (VUS). Whether the de novoATP1A3mutation is responsible for or plays a role in the patient's episodes of fatigue and somnolence remains to be determined. The unprecedented combination of two NLRP3 mutations may be responsible for other aspects of his complex phenotype.
  • Thumbnail Image
    Publication
    N100 Repetition Suppression Indexes Neuroplastic Defects in Clinical High Risk and Psychotic Youth
    (Hindawi Publishing Corporation, 2016) Gonzalez-Heydrich, Joseph; Bosquet Enlow, Michelle; D'Angelo, Eugene; Seidman, Larry Joel; Gumlak, Sarah; Kim, April; Woodberry, Kristen; Rober, Ashley; Tembulkar, Sahil; O'Donnell, Kyle; Hamoda, Hesham; Kimball, Kara; Rotenberg, Alexander; Oberman, Lindsay M.; Pascual-Leone, Alvaro; Keshavan, Matcheri; Duffy, Frank
    Highly penetrant mutations leading to schizophrenia are enriched for genes coding for N-methyl-D-aspartate receptor signaling complex (NMDAR-SC), implicating plasticity defects in the disease's pathogenesis. The importance of plasticity in neurodevelopment implies a role for therapies that target these mechanisms in early life to prevent schizophrenia. Testing such therapies requires noninvasive methods that can assess engagement of target mechanisms. The auditory N100 is an obligatory cortical response whose amplitude decreases with tone repetition. This adaptation may index the health of plasticity mechanisms required for normal development. We exposed participants aged 5 to 17 years with psychosis (n = 22), at clinical high risk (CHR) for psychosis (n = 29), and healthy controls (n = 17) to an auditory tone repeated 450 times and measured N100 adaptation (mean amplitude during first 150 tones − mean amplitude during last 150 tones). N100 adaptation was reduced in CHR and psychosis, particularly among participants <13 years old. Initial N100 blunting partially accounted for differences. Decreased change in the N100 amplitude with tone repetition may be a useful marker of defects in neuroplastic mechanisms measurable early in life.