Kathleen Rooney
A5091347040- Epigenetics and DNA Methylation
- Genetics and Neurodevelopmental Disorders
- Genomic variations and chromosomal abnormalities
- Genomics and Rare Diseases
- Cancer-related gene regulation
- Genetic Syndromes and Imprinting
- Williams Syndrome Research
- Reproductive Biology and Fertility
- RNA regulation and disease
- RNA Research and Splicing
- Peptidase Inhibition and Analysis
- RNA modifications and cancer
- Congenital gastrointestinal and neural anomalies
- Tissue Engineering and Regenerative Medicine
- Autism Spectrum Disorder Research
- Genetic factors in colorectal cancer
- Congenital heart defects research
- Tracheal and airway disorders
- ATP Synthase and ATPases Research
- Chromatin Remodeling and Cancer
London Health Sciences Centre
2021-2025
Western University
2021-2024
Pitié-Salpêtrière Hospital
2023
Sorbonne Université
2023
University of Amsterdam
2023
Overlapping clinical phenotypes and an expanding breadth complexity of genomic associations are a growing challenge in the diagnosis management Mendelian disorders. The functional consequences impacts variation may involve unique, disorder-specific, DNA methylation episignatures. In this study, we describe 19 novel episignature disorders compare findings alongside 38 previously established episignatures for total 57 associated with 65 genetic syndromes. We demonstrate increasing resolution...
An expanding range of genetic syndromes are characterized by genome-wide disruptions in DNA methylation profiles referred to as episignatures. Episignatures distinct, highly sensitive, and specific biomarkers that have recently been applied clinical diagnosis syndromes. contained within the broader disorder-specific changes, which can share significant overlap among different conditions. In this study, we performed functional genomic assessment comparison overlapping changes related 65 with...
SRSF1 (also known as ASF/SF2) is a non-small nuclear ribonucleoprotein (non-snRNP) that belongs to the arginine/serine (R/S) domain family. It recognizes and binds mRNA, regulating both constitutive alternative splicing. The complete loss of this proto-oncogene in mice embryonically lethal. Through international data sharing, we identified 17 individuals (10 females 7 males) with neurodevelopmental disorder (NDD) heterozygous germline variants, mostly de novo, including three frameshift...
Phelan-McDermid syndrome is characterized by a range of neurodevelopmental phenotypes with incomplete penetrance and variable expressivity. It caused size breakpoint microdeletions in the distal long arm chromosome 22, referred to as 22q13.3 deletion syndrome, including SHANK3 gene. Genetic defects growing number genes have been shown cause genome-wide disruptions epigenomic profiles epi-signatures affected individuals. In this study we assessed DNA methylation cohort 22 individuals 11 large...
Rare genetic variants in ARID2 are responsible for a recently described neurodevelopmental condition called ARID2-related disorder (ARID2-RD). belongs to PBAF, unit of the SWI/SNF complex, which is chromatin remodeling complex. This work aims further delineate phenotypic spectrum ARID2-RD, providing clinicians with additional data better care and aid future diagnosis this condition. We obtained genotypes phenotypes 27 previously unreported individuals ARID2-RD compared series findings...
PurposeThis study aimed to undertake a multidisciplinary characterization of the phenotype associated with SOX11 variants.MethodsIndividuals protein altering variants in were identified through exome and genome sequencing international data sharing. Deep clinical phenotyping was undertaken by referring clinicians. Blood DNA methylation assessed using Infinium MethylationEPIC array. The expression pattern developing human brain defined RNAscope.ResultsWe reported 38 new patients variants....
The 22q11.2 deletion syndrome (22q11.2DS) is the most common genomic disorder in humans and result of a recurrent 1.5 to 2.5 Mb deletion, encompassing approximately 20–40 genes, respectively. clinical presentation typical includes: Velocardiofacial, Di George, Opitz G/BBB Conotruncalanomaly face syndromes. Atypical deletions (proximal, distal or nested) are rare characterized mainly by normal phenotype mild intellectual disability variable features. pathogenetic mechanisms underlying this...
Abstract Chung-Jansen syndrome is a neurodevelopmental disorder characterized by intellectual disability, behavioral problems, obesity and dysmorphic features. It caused pathogenic variants in the PHIP gene that encodes for Pleckstrin homology domain-interacting protein, which part of an epigenetic modifier protein complex. Therefore, we hypothesized haploinsufficiency may impact genome-wide DNA methylation (DNAm). We assessed DNAm profiles affected individuals with likely Infinium...
Abstract Mowat-Wilson syndrome (MOWS) is a rare congenital disease caused by haploinsufficiency of ZEB2 , encoding transcription factor required for neurodevelopment. MOWS characterized intellectual disability, epilepsy, typical facial phenotype and other anomalies, such as short stature, Hirschsprung disease, brain heart defects. Despite some recognizable features, rarity phenotypic variability may complicate its diagnosis, particularly in the neonatal period. In order to define novel...
JARID2 (Jumonji, AT Rich Interactive Domain 2) pathogenic variants cause a neurodevelopmental syndrome, that is characterized by developmental delay, cognitive impairment, hypotonia, autistic features, behavior abnormalities and dysmorphic facial features. encodes transcriptional repressor protein regulates the activity of various histone methyltransferase complexes. However, molecular etiology not fully understood, JARID2-neurodevelopmental syndrome may vary in its typical clinical...
Clark-Baraitser syndrome is a rare autosomal dominant intellectual disability caused by pathogenic variants in the TRIP12 (Thyroid Hormone Receptor Interactor 12) gene. encodes an E3 ligase ubiquitin pathway. The pathway includes activating E1, conjugating E2 and ligating enzymes which regulate breakdown sorting of proteins. This enzymatic crucial for physiological processes. A significant proportion are currently classified as unknown significance (VUS). Episignatures have been shown to...
Abstract Precise regulation of gene expression is important for correct neurodevelopment. 9q34.3 deletions affecting the EHMT1 result in a syndromic neurodevelopmental disorder named Kleefstra syndrome. In contrast, duplications locus encompassing have been suggested to cause developmental disorders, but only limited information has available. We identified 15 individuals from 10 unrelated families, with <1.5 Mb size, entirely. Clinical features included mild delay, intellectual...
JARID2 (Jumonji, AT-rich interactive domain 2) haploinsufficiency is associated with a clinically distinct neurodevelopmental syndrome. It characterized by intellectual disability, developmental delay, autistic features, behavior abnormalities, cognitive impairment, hypotonia, and dysmorphic features. acts as transcriptional repressor protein that involved in the regulation of histone methyltransferase complexes. plays role epigenetic machinery, syndrome has an identified DNA methylation...
Neurodevelopmental disorder with or without autism seizures (NEDAUS) is a neurodevelopmental characterized by global developmental delay, speech seizures, autistic features, and/or behavior abnormalities. It caused CUL3 (Cullin-3 ubiquitin ligase) haploinsufficiency. We collected clinical and molecular data from 26 individuals carrying pathogenic variants of uncertain significance (VUS) in the gene, including 20 previously unreported cases. By comparing their DNA methylation (DNAm)...
Hereditary cancer predisposition syndromes account for approximately 10% of cases. Next generation sequencing (NGS) based multi-gene targeted panels is now a frontline approach to identify pathogenic mutations in genes high-risk families. Recent evolvement NGS technologies have allowed simultaneous detection sequence and copy number variants (CNVs) using single platform. In this study, we analyzed frequency nature CNVs, Canadian cohort patients, suspected with hereditary syndrome, referred...