Jennifer Kerkhof
A5047369065- Epigenetics and DNA Methylation
- Genetics and Neurodevelopmental Disorders
- Genomics and Rare Diseases
- Genomic variations and chromosomal abnormalities
- Chromatin Remodeling and Cancer
- Cancer-related gene regulation
- Genetic Syndromes and Imprinting
- Cancer Genomics and Diagnostics
- RNA modifications and cancer
- Genomics and Chromatin Dynamics
- Genetic factors in colorectal cancer
- BRCA gene mutations in cancer
- Congenital heart defects research
- Tracheal and airway disorders
- Immunodeficiency and Autoimmune Disorders
- Autism Spectrum Disorder Research
- Oral and gingival health research
- Acute Myeloid Leukemia Research
- Congenital limb and hand anomalies
- Peptidase Inhibition and Analysis
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Bone health and osteoporosis research
- Nuclear Structure and Function
- Cancer Mechanisms and Therapy
- Bone Metabolism and Diseases
London Health Sciences Centre
2016-2025
Western University
2018-2025
University of Wisconsin–Madison
2024
Hanover College
2024
Victoria Hospital
2019-2020
Laboratory of Molecular Genetics
2020
Children’s Health Research Institute
2016-2020
St Joseph's Health Care
2018
Erasmus MC
2008
Erasmus University Rotterdam
2008
PurposeWe describe the clinical implementation of genome-wide DNA methylation analysis in rare disorders across EpiSign diagnostic laboratory network and assessment results impact first subjects tested.MethodsWe outline logistics data flow between an integrated diagnostics laboratories Europe, United States, Canada. We validation using 211 specimens assess test performance yield 207 tested involving two patient subgroups: targeted cohort (subjects with previous ambiguous/inconclusive genetic...
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...
ADNP syndrome is a rare Mendelian disorder characterized by global developmental delay, intellectual disability, and autism. It caused truncating mutations in ADNP, which involved chromatin regulation. We hypothesized that the disruption of regulation might result specific DNA methylation patterns could be used molecular diagnosis syndrome. identified two distinct partially opposing genomic episignatures peripheral blood samples from 22 patients with The "epi-ADNP-1" episignature included ~...
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...
<h3>Background:</h3> A polymorphism (rs143383; T to C) near the <i>GDF5</i> gene has been associated with height and osteoarthritis (OA), but debate exists about whether its primary biological action is directed cartilage or bone. <h3>Objective:</h3> To study association between genetic variation in region radiographic (ROA) susceptibility, height, bone size parameters fracture risk a large population-based cohort of Caucasian elderly subjects. <h3>Methods:</h3> 6365 men women had genotype...
Abstract Background We previously associated HIST1H1E mutations causing Rahman syndrome with a specific genome-wide methylation pattern. Results Methylome analysis from peripheral blood samples of six affected subjects led us to identify hypomethylated profile. This “episignature” was enriched for genes involved in neuronal system development and function. A computational classifier yielded full sensitivity specificity detecting syndrome. Applying this model cohort undiagnosed probands...
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...
Abstract Neurodevelopmental disorders (NDDs) result from impaired development and functioning of the brain. Here, we identify loss-of-function variation in ZFHX3 as a novel cause for syndromic intellectual disability (ID). ZFHX3, previously known ATBF1, is zinc-finger homeodomain transcription factor involved multiple biological processes including cell differentiation tumorigenesis. Through international collaboration, collected clinical morphometric data (Face2Gene) 41 individuals with...
Abstract Sequence-based genetic testing identifies causative variants in ~ 50% of individuals with developmental and epileptic encephalopathies (DEEs). Aberrant changes DNA methylation are implicated various neurodevelopmental disorders but remain unstudied DEEs. We interrogate the diagnostic utility genome-wide array analysis on peripheral blood samples from 582 genetically unsolved identify rare differentially methylated regions (DMRs) explanatory episignatures to uncover candidate...
Over two decades ago, a primigravid female presented with concern for recurrence of an adverse phenotype affecting her three brothers. The brothers intellectual disability, developmental delay, behavior problems and dysmorphic features. screening tools available at the time revealed FGD1 variant present in all brothers, their mother being carrier, absent unaffected uncle, proband herself. This was hypothesized to be explanatory, but years later more advanced genetic showed that it benign....
ABSTRACT SETD2 has an essential role in epigenetic regulation. pathogenic variants cause neurodevelopmental disorders ( ‐NDDs) that most commonly include various degrees of intellectual disability and behavioral disorders, macrocephaly, brain malformations, generalized overgrowth. A distinctive DNA methylation episignature been identified for Luscan–Lumish syndrome. less common phenotype, denoted ‐NDD with multiple congenital anomalies, failure to thrive, profound disability, reported...
PurposePathogenic variants in SETD1B have been associated with a syndromic neurodevelopmental disorder including intellectual disability, language delay, and seizures. To date, clinical features described for 11 patients (likely) pathogenic sequence variants. This study aims to further delineate the spectrum of SETD1B-related syndrome based on characterizing an expanded patient cohort.MethodsWe perform in-depth characterization cohort 36 unpublished individuals variants, describing their...