A5021150258- Genomic variations and chromosomal abnormalities
- Genomics and Rare Diseases
- Genetics and Neurodevelopmental Disorders
- Prenatal Screening and Diagnostics
- Congenital heart defects research
- Autism Spectrum Disorder Research
- Metabolism and Genetic Disorders
- Cancer Genomics and Diagnostics
- Hedgehog Signaling Pathway Studies
- Neuroendocrine regulation and behavior
- BRCA gene mutations in cancer
- Bioinformatics and Genomic Networks
- Genomics and Chromatin Dynamics
- Chromosomal and Genetic Variations
- Stress Responses and Cortisol
- Epigenetics and DNA Methylation
- CRISPR and Genetic Engineering
- Radiomics and Machine Learning in Medical Imaging
- Muscle metabolism and nutrition
- Protein Tyrosine Phosphatases
- Congenital gastrointestinal and neural anomalies
- Recreation, Leisure, Wilderness Management
- Mitochondrial Function and Pathology
- Disability Education and Employment
- Biomedical Ethics and Regulation
BioNano Genomics (United States)
2021-2022
Lineage Cell Therapeutics (United States)
2013-2020
University of Utah
2011-2019
University of Toronto
2019
Hospital for Sick Children
2019
SickKids Foundation
2019
University of Wisconsin–Madison
2005-2006
<h3>Background</h3> We aimed for a comprehensive delineation of genetic, functional and phenotypic aspects <i>GRIN2B</i> encephalopathy explored potential prospects personalised medicine. <h3>Methods</h3> Data 48 individuals with de novo variants were collected from several diagnostic research cohorts, as well 43 patients the literature. Functional consequences response to memantine treatment investigated in vitro eventually translated into patient care. <h3>Results</h3> Overall, 86...
Abstract While exome sequencing (ES) is commonly the final diagnostic step in clinical genetics, it may miss diagnoses. To clarify limitations of ES, we investigated yield genetic tests beyond ES our Undiagnosed Diseases Network (UDN) participants. We reviewed additional testing including genome (GS), copy number variant (CNV), noncoding (NCV), repeat expansion (RE), or methylation UDN cases with nondiagnostic results. Overall, 36/54 (67%) total diagnoses were based on findings and coding...
Abstract Creatine is a nitrogen containing compound that serves as an energy shuttle between the mitochondrial sites of ATP production and cytosol where utilized. There are two known disorders creatine synthesis (both transmitted autosomal recessive traits: arginine: glycine amidinotransferase (AGAT) deficiency; OMIM 602360; guanidinoacetate methyltransferase (GAMT) deficiency (OMIM 601240)) one disorder transport (X‐linked SLC6A8 transporter 300036)). All these characterized by brain...
Copy number variants (CNVs) detected by chromosomal microarray analysis (CMA) significantly contribute to understanding the etiology of autism spectrum disorder (ASD) and other related conditions. In recognition value CMA testing its impact on medical management, is in guidelines as a first-tier test evaluation children with these disorders. As becomes adopted into routine care for patients, it increasingly important report clinical findings. This study summarizes results over 4 years...
<h3>Background</h3> Wolf–Hirschhorn syndrome (WHS) is a contiguous gene deletion involving variable size deletions of the 4p16.3 region. Seizures are frequently, but not always, associated with WHS. We hypothesised that and location deleted region may correlate seizure presentation. <h3>Methods</h3> Using chromosomal microarray analysis, we finely mapped breakpoints copy number variants (CNVs) in 48 individuals Seizure phenotype data were collected through parent-reported answers to...
We previously applied selective breeding on outbred mice to increase maternal aggression (maternal defense). In this study, we compared gene expression within a continuous region of the central nervous system (CNS) involved in (hypothalamus and preoptic regions) between lactating selected (S) nonselected control (C) (n= 6 per group). Using microarrays representing over 40,000 genes or expressed sequence tags, two statistical algorithms were used identify significant differences expression:...
Copy number variants (CNVs) as detected by chromosomal microarray analysis (CMA) significantly contribute to the etiology of neurodevelopmental disorders, such developmental delay (DD), intellectual disability (ID), and autism spectrum disorder (ASD). This study summarizes results 3.5 years CMA testing a CLIA-certified clinical laboratory 5487 patients with conditions were clinically evaluated for rare copy using 2.8-million probe custom optimized detection CNVs associated disorders. We...
Chromosomal microarray analysis (CMA) is recommended as the first-tier clinical diagnostic test for individuals with developmental disabilities. In addition to detecting copy number variations, CMA platforms single nucleotide polymorphism probes can detect large homozygous regions within genome, which represent potential risk recessively inherited disorders. To determine frequency in pathogenic or likely variants be detected these of homozygosity, we performed whole exome sequencing (WES) 53...
Copy number variants (CNV)s involving KANK1 are generally classified as of unknown significance. Several clinical case reports suggest that the loss on chromosome 9p24.3 has potential impact neurodevelopment. These studies inconsistent in terms patient phenotype and suspected pattern inheritance. Further complexities arise because these published utilize a variety genetic testing platforms with varying resolution 9p region; this ultimately causes uncertainty about impacted genomic...
Mosaic chromosomal abnormalities are relatively common. However, mosaicism may be missed due to multiple factors including failure recognize clinical indications and order appropriate testing, technical limitations of diagnostic assays, or sampling tissue (s) in which is either not present, present at very low levels. Blood leukocytes have long been the "gold standard" sample for cytogenetic analysis; however, culturing process routine chromosome analysis can complicate detection since...
Mowat-Wilson syndrome is a rare genetic condition characterized by intellectual disability, structural anomalies, and dysmorphic features. It caused haploinsufficiency of the <i>ZEB2</i> gene in chromosome 2q22.3. Over 180 distinct mutations have been reported, including nonsense missense point mutations, deletions, large chromosomal rearrangements. We report on 14-year-old female with clinical diagnosis syndrome. Chromosomal microarray identified novel de novo 69-kb duplication...
The steroid sensitive vasopressin cells of the bed nucleus stria terminalis (BST) and centromedial amygdala (CMA) are involved in numerous behavioural physiological functions. These known to be greatly influenced by gonadal steroids. Castration reduces testosterone replacement restores arginine (AVP)-immunoreactive (-ir) labelling AVP mRNA expression BST CMA. Gonadal steroids appear act directly AVP-expressing within CMA, because majority AVP-ir these areas contain oestrogen androgen...
Abstract In 2016, Methylation-Specific Quantitative Melt Analysis (MS-QMA) on 3,340 male probands increased diagnostic yield from 1.60% to 1.84% for fragile X syndrome (FXS) using a pooling approach. this study Lineagen (UT, U.S.A.) of both sexes were screened MS-QMA without sample pooling. The cohorts included: (i) 279 with no FXS full mutation (FM: CGG > 200) detected by AmplideX sizing; (ii) 374 negative and 47 positive controls. sensitivity specificity in controls approached 100%...
We report on a unique case of mosaic 20pter‐p13 deletion due to somatic repair event identified by allele differentiating single nucleotide polymorphism (SNP) probes chromosomal microarray. Small terminal deletions 20p have been reported in few individuals and appear result variable phenotype. This patient was 24‐month‐old female who presented with failure thrive speech delay. Chromosomal microarray analysis (CMA) performed peripheral blood showed 1.6 Mb involving the terminus...
Chromosomal microarray analysis (CMA) is recognized as the first-tier test in genetic evaluation of children with developmental delays, intellectual disabilities, congenital anomalies and autism spectrum disorders unknown etiology.To optimize detection clinically relevant copy number variants associated these conditions, we designed a whole-genome microarray, FirstStepDx PLUS (FSDX). A set 88,435 custom probes was added to Affymetrix CytoScanHD platform targeting genomic regions strongly...
Autism spectrum disorder (ASD) is a heterogeneous condition with complex genetic etiology. The objective of this study to identify the factors that underlie ASD phenotype and other clinical features Professor Temple Grandin, an animal scientist woman high-functioning ASD. Identifying underlying cause for can impact medical management, personalize services treatment, uncover risks are associated diagnosis. Prof. Grandin underwent chromosomal microarray analysis, whole exome sequencing, genome...
Developmental disorders (DD), including autism spectrum disorder (ASD) and intellectual disability (ID), are a common group of clinical manifestations caused by variety genetic abnormalities. Genetic testing, chromosomal microarray (CMA), plays an important role in diagnosing these conditions, but CMA can be limited incomplete coverage abnormalities lack guidance for conditions rarely seen treating physicians.We conducted longitudinal, randomized controlled trial investigating the impact...
To evaluate a new tool to aid interpretation of copy number variants (CNVs) in individuals with neurodevelopmental disabilities.Critical exon indexing (CEI) was used identify genes critical exons (CEGs) from clinically reported CNVs, which may contribute disorders (NDDs). The 742 pathogenic CNVs and 1,363 unknown significance (VUS) identified by chromosomal microarray analysis 5,487 NDDs were subjected CEI CEGs. CEGs subsequent random series VUS evaluated for relevance CNV interpretation.CEI...