A5019288569- Metabolism and Genetic Disorders
- Mitochondrial Function and Pathology
- Genomics and Chromatin Dynamics
- Genomic variations and chromosomal abnormalities
- Diet and metabolism studies
- Amino Acid Enzymes and Metabolism
- Telomeres, Telomerase, and Senescence
- Biochemical and Molecular Research
- Ion Transport and Channel Regulation
- Biochemical Acid Research Studies
- Neonatal Health and Biochemistry
- Genetics and Neurodevelopmental Disorders
- DNA Repair Mechanisms
- Pancreatic function and diabetes
- Invertebrate Immune Response Mechanisms
- Functional Brain Connectivity Studies
- Genomics and Rare Diseases
- RNA modifications and cancer
- Hyperglycemia and glycemic control in critically ill and hospitalized patients
- Lymphatic System and Diseases
- Bipolar Disorder and Treatment
- Genetic Syndromes and Imprinting
- Metabolomics and Mass Spectrometry Studies
- Cancer Research and Treatments
- Peroxisome Proliferator-Activated Receptors
Children's Hospital of Pittsburgh
2007-2024
University of Pittsburgh
2007-2024
Center for Human Genetics
2014-2021
University Hospitals of Cleveland
2016-2021
Case Western Reserve University
2015-2021
Rainbow Babies & Children's Hospital
2019-2021
Columbia University Irving Medical Center
2020
Radboud University Nijmegen
2020
Radboud University Medical Center
2020
Center for Inherited Blood Disorders
2020
Short-chain enoyl-CoA hydratase (SCEH, encoded by ECHS1) catalyzes hydration of 2-trans-enoyl-CoAs to 3(S)-hydroxy-acyl-CoAs. SCEH has a broad substrate specificity and is believed play an important role in mitochondrial fatty acid oxidation the metabolism branched-chain amino acids. Recently, first patients with deficiency have been reported revealing only defect valine catabolism. We investigated four newly identified patients. In addition, because Leigh-like presentation, we studied...
Objective Individuals with urea cycle disorders (UCDs) often present intellectual and developmental disabilities. The major aim of this study was to evaluate the impact diagnostic therapeutic interventions on cognitive outcomes in UCDs. Methods This prospective, observational, multicenter includes data from 503 individuals UCDs who had comprehensive neurocognitive testing a cumulative follow‐up 702 patient‐years. Results mean standard deviation score (cSDS) lower symptomatic than...
To describe clinical, biochemical, and genetic features of participants with mitochondrial diseases (MtDs) enrolled in the North American Mitochondrial Disease Consortium (NAMDC) Registry.This cross-sectional, multicenter, retrospective database analysis evaluates phenotypic molecular characteristics NAMDC Registry from September 2011 to December 2018. The is a network 17 centers expertise MtDs includes both adult pediatric specialists.One thousand four hundred ten 1,553 had sufficient...
Abstract Submicroscopic recurrent 16p11.2 rearrangements are associated with several neurodevelopmental disorders, including autism, mental retardation, and schizophrenia. The common region includes 24 known genes, of which 22 expressed in the developing human fetal nervous system. As yet, mechanisms leading to abnormalities broader phenotypes deletion or duplication have not been clarified. Here we report a child spastic quadriparesis, refractory infantile seizures, severe global...
Abstract We report on a 26‐month‐old boy with developmental delay and multiple congenital anomalies, including many features suggestive of either branchiootorenal syndrome (BOR) or oculoauriculovertebral spectrum (OAVS). Chromosomal microarray analysis (CMA) initially revealed copy‐number gain single BAC clone (RP11‐79M1) mapping to 14q23.1. FISH showed that the third copy this genomic region was inserted into long arm one chromosome 13. The same pattern also seen in chromosomes father, who...
Background The aim of this report was to present a rare case an adolescent with multinodular goiter (MNG) found have DICER1 mutation. Methods and Results methodology includes presentation discussion chart review including endocrine hormone tests, thyroid ultrasound, genetic testing for . A 12‐year‐old girl presented diffusely enlarged gland. Family history revealed older sister bilateral ovarian Sertoli‐Leydig cell tumors MNG. Thyroid function tests were normal. Serial ultrasounds showed...
Abstract Argininosuccinate lyase (ASL) is essential for the NO-dependent regulation of tyrosine hydroxylase (TH) and thus catecholamine production. Using a conditional mouse model with loss ASL in neurons, we demonstrate that expressed dopaminergic neurons substantia nigra pars compacta, including ALDH1A1 + subpopulation pivotal pathogenesis Parkinson disease (PD). Neuronal results deficiency, accumulation formation aggregates, elevation α-synuclein, phenotypically motor cognitive deficits....
The S and L G alleles of the serotonin transporter‐linked polymorphic region (5‐HTTLPR) lower transporter expression. These low‐expressing are linked to increased risk for depression brain activation patterns found in (increased amygdala decreased amygdala–prefrontal cortex connectivity). Paradoxically, blockade relieves symptoms. Rodent models suggest that early life produces emerges adolescence, whereas occurs later development ameliorates depression. However, no imaging research has yet...
Argininosuccinic aciduria (ASA) is an inherited urea cycle disorder and has a highly variable phenotypic spectrum ranging from individuals with lethal hyperammonemic encephalopathy, liver dysfunction, cognitive deterioration, to mild disease course. As it difficult predict the severity, we aimed at identifying reliable prediction model. We applied biallelic expression system assess functional impact of pathogenic argininosuccinate lyase (ASL) variants determine enzymatic activity ASL in 58...
The question of whether excision repair yeast plasmids accurately reflects the genomic chromatin has yielded conflicting answers. These conflicts could have arisen from differences in conformation plasmid molecules used during these studies. We examined UV photoproducts a small (2619 bp) autonomously replicating (YRp-TRURAP), known to be folded into with positioned nucleosomes vivo , In Saccharomyces cerevisiae . A quantitative assay was measure yield cyclobutane pyrimidine dimers (PD) DNA...
Abstract Low protein diet and sodium or glycerol phenylbutyrate, two pillars of recommended long-term therapy individuals with urea cycle disorders (UCDs), involve the risk iatrogenic growth failure. Limited evidence-based studies hamper our knowledge on effects proposed medical management in UCDs. We studied impact weight development 307 longitudinally followed by Urea Cycle Disorders Consortium (UCDC) European registry network for Intoxication type Metabolic Diseases (E-IMD). Intrauterine...
Vertebrate telomeres contain arrays of nucleosomes with unusually short and regular repeat lengths (Makarov, V. L., Lejnine, S., Bedoyan, J., Langmore, J. P. (1993) Cell 73, 775-787; Makarov, V., (1995) Proc. Natl. Acad. Sci. U. S. A. 92, 2393-2397). In order to better define the specific structural features telomere chromatin, we examined condensation H1 content nucleoproteins from rat liver. Velocity sedimentation analysis shows that telomeric nucleosome condense increasing ionic strength...
ND, not determined.The half-life of this RNA is estimated to be >150 min, and the relative rate synthesis cO.1 min" X 10' (see "Results").
Martin--Probst syndrome (MPS) is a rare X-linked disorder characterised by deafness, cognitive impairment, short stature and distinct craniofacial dysmorphisms, among other features. The authors sought to identify the causative mutation for MPS.Massively parallel sequencing in two affected, related male subjects with MPS identified RAB40AL (also called RLGP) missense (chrX:102,079,078-102,079,079AC→GA p.D59G; hg18). encodes small Ras-like GTPase protein one suppressor of cytokine signalling...