We recruit patients and families with rare genetic diseases, and try to solve the underlying genetic cause by finding different mutations in the same gene among unrelated families with similar diseases.
We have been successful in finding mutations in major “epigenes” – these are genes that code for proteins that open DNA up to activate it, or close it down to keep it quiet. We hope that the rare syndromes we have described will help us learn how these epigenetic programs can increase or decrease the risks for common diseases in the general population.
Mutations in EZH2 cause weaver syndrome
American Journal of Human Genetics
DOI: 10.1016/j.ajhg.2011.11.018
2012
A novel mutation in EED associated with overgrowth
Journal of Human Genetics
DOI: 10.1038/jhg.2015.26
2015
EED-associated overgrowth in a second male patient
Journal of Human Genetics
DOI: 10.1038/jhg.2016.51
2016
Weaver Syndrome-Associated EZH2 Protein Variants Show Impaired Histone Methyltransferase Function In Vitro
Human Mutation
DOI: 10.1002/humu.22946
2016
A Review of the Genetics of Intracranial Berry Aneurysms and Implications for Genetic Counseling
Journal of Genetic Counseling
DOI: 10.1007/s10897-016-0029-8
2017
A systematic review of genetic syndromes with obesity
Obesity Reviews
DOI: 10.1111/obr.12531
2017
Severe obesity and global developmental delay in preschool children
11/2018
MN1 C-terminal truncation syndrome is a novel neurodevelopmental and craniofacial disorder with partial rhombencephalosynapsis.
Brain : a journal of neurology
DOI: 10.1093/brain/awz379
PubMed: 31834374
01/2020
Rare SUZ12 variants commonly cause an overgrowth phenotype.
American journal of medical genetics. Part C, Seminars in medical genetics
DOI: 10.1002/ajmg.c.31748
PubMed: 31736240
11/2019
PRC2-complex related dysfunction in overgrowth syndromes: A review of EZH2, EED, and SUZ12 and their syndromic phenotypes.
American journal of medical genetics. Part C, Seminars in medical genetics
DOI: 10.1002/ajmg.c.31754
PubMed: 31724824
11/2019
Two Patients With KCNT1-Related Epilepsy Responding to Phenobarbital and Potassium Bromide.
Journal of child neurology
DOI: 10.1177/0883073819854853
PubMed: 31208268
06/2019
A distinct neurodevelopmental syndrome with intellectual disability, autism spectrum disorder, characteristic facies, and macrocephaly is caused by defects in CHD8.
Journal of human genetics
DOI: 10.1038/s10038-019-0561-0
PubMed: 30670789
01/2019
TSC2 c.1864C>T variant associated with mild cases of tuberous sclerosis complex
American Journal of Medical Genetics, Part A
DOI: 10.1002/ajmg.a.38083
2017
A maternal high-fat, high-sucrose diet has sex-specific effects on fetal glucocorticoids with little consequence for offspring metabolism and voluntary locomotor activity in mice
PLoS ONE
DOI: 10.1371/journal.pone.0174030
2017
Absence of mutations in HCRT , HCRTR1 and HCRTR2 in patients with ROHHAD
Respiratory Physiology & Neurobiology
Sarah F. Barclay and Casey M. Rand and Paul A. Gray and William T. Gibson and Richard J.A. Wilson and Elizabeth M. Berry-Kravis and Diego Ize-Ludlow and N. Torben Bech-Hansen and Debra E. Weese-Mayer
DOI: 10.1016/j.resp.2015.11.002
01/2016
Mutations in FLNC are Associated with Familial Restrictive Cardiomyopathy
Human Mutation
DOI: 10.1002/humu.22942
2016
Core Concepts in Human Genetics: Understanding the Complex Phenotype of Sport Performance and Susceptibility to Sport Injury
Medicine and Sport Science
DOI: 10.1159/000445237
2016
Ghrelin, Ghrelin O-Acyltransferase, and Carbohydrate Metabolism During Pregnancy in Calorie-Restricted Mice
Hormone and Metabolic Research
DOI: 10.1055/s-0042-116117
2016
A novel microdeletion affecting the CETP gene raises HDL-associated cholesterol levels
Clinical Genetics
DOI: 10.1111/cge.12633
2016
Utility of whole-exome sequencing for those near the end of the diagnostic odyssey: Time to address gaps in care
Clinical Genetics
DOI: 10.1111/cge.12654
2016
Acylated ghrelin is not required for the surge in pituitary growth hormone observed in pregnant mice
Peptides
DOI: 10.1016/j.peptides.2015.01.005
03/2015
Leptin and adiponectin: Examining their clinical significance in obesity
University of Toronto Medical Journal
2015
Vasoactive intestinal polypeptide promotes intestinal barrier homeostasis and protection against colitis in mice
PLoS ONE
DOI: 10.1371/journal.pone.0125225
2015
Rapid-Onset Obesity with Hypothalamic Dysfunction, Hypoventilation, and Autonomic Dysregulation (ROHHAD): Exome sequencing of trios, monozygotic twins and tumours
Orphanet Journal of Rare Diseases
DOI: 10.1186/s13023-015-0314-x
2015
Episodic ataxia associated with a de novo SCN2A mutation
European Journal of Paediatric Neurology
DOI: 10.1016/j.ejpn.2016.05.020
2015
A high-fat diet rich in corn oil reduces spontaneous locomotor activity and induces insulin resistance in mice
Journal of Nutritional Biochemistry
DOI: 10.1016/j.jnutbio.2014.11.004
2015
Beneficial metabolic phenotypes caused by loss-of-function APOC3 mutations
Clinical Genetics
DOI: 10.1111/cge.12483
2015
NSD1 mutations generate a genome-wide DNA methylation signature
Nature Communications
DOI: 10.1038/ncomms10207
2015
Alternating hypoglycemia and hyperglycemia in a toddler with a homozygous p.R1419H ABCC8 mutation: An unusual clinical picture
Journal of Pediatric Endocrinology and Metabolism
DOI: 10.1515/jpem-2014-0265
2015
Autosomal dominant PIK3R1 mutations cause SHORT syndrome
Clinical Genetics
DOI: 10.1111/cge.12262
2014
Biallelic mutations at PPARG cause a congenital, generalized lipodystrophy similar to the Berardinelli-Seip syndrome
European Journal of Medical Genetics
DOI: 10.1016/j.ejmg.2014.06.006
2014
Genetic Counseling in Direct-to-Consumer Exome Sequencing: A Case Report
Journal of Genetic Counseling
DOI: 10.1007/s10897-014-9737-0
2014
Somatic mosaicism for the p.His1047Arg mutation in PIK3CA in a girl with mesenteric lipomatosis
American Journal of Medical Genetics, Part A
DOI: 10.1002/ajmg.a.36622
2014
Duplication of AKT3 is associated with macrocephaly and speech delay
American Journal of Medical Genetics, Part A
DOI: 10.1002/ajmg.a.36521
2014
Exome sequencing identifies mutations in KIF14 as a novel cause of an autosomal recessive lethal fetal ciliopathy phenotype
Clinical Genetics
DOI: 10.1111/cge.12301
2014
Mutations in POLR3A and POLR3B are a major cause of hypomyelinating leukodystrophies with or without dental abnormalities and/or hypogonadotropic hypogonadism
Journal of Medical Genetics
DOI: 10.1136/jmedgenet-2012-101357
2013
The c.7409G>A (p.Cys2470Tyr) variant of FBN1: Phenotypic variability across three generations
Molecular Syndromology
DOI: 10.1159/000347163
2013
Mutations in EZH2 Cause Weaver Syndrome.
12/2011
Acute disruption of leptin signaling in vivo leads to increased insulin levels and insulin resistance
Endocrinology
DOI: 10.1210/en.2011-0185
2011
Duchenne muscular dystrophy caused by a complex rearrangement between intron 43 of the DMD gene and chromosome 4
Neuromuscular Disorders
DOI: 10.1016/j.nmd.2010.11.008
2011
Effects of glucose and insulin on acyl ghrelin and desacyl ghrelin, leptin, and adiponectin in pregnant women with diabetes
Metabolism: Clinical and Experimental
DOI: 10.1016/j.metabol.2009.09.033
2010
The metabolic phenotype of SCD1-deficient mice is independent of melanin-concentrating hormone
Peptides
DOI: 10.1016/j.peptides.2009.10.018
2010
Pseudohypoparathyroidism type 1a and the GNAS p.R231H mutation: Somatic mosaicism in a mother with two affected sons
American Journal of Medical Genetics, Part A
DOI: 10.1002/ajmg.a.33172
2010
Ldlr-/- mice display decreased susceptibility to western-type diet-induced obesity due to increased thermogenesis
Endocrinology
DOI: 10.1210/en.2010-0496
2010
Clinical study of two brothers with a novel 33 bp duplication in the ARX gene
American Journal of Medical Genetics, Part A
DOI: 10.1002/ajmg.a.32851
2009
Key concepts in human genetics: Understanding the complex phenotype
Medicine and Sport Science
DOI: 10.1159/000235693
2009
Genetic association studies for complex traits: Relevance for the sports medicine practitioner
British Journal of Sports Medicine
DOI: 10.1136/bjsm.2008.052191
2009
Detection of pathogenic copy number variants in children with idiopathic intellectual disability using 500 K SNP array genomic hybridization
BMC Genomics
DOI: 10.1186/1471-2164-10-526
2009
Absence of stearoyl-CoA desaturase-1 ameliorates features of the metabolic syndrome in LDLR-deficient mice
Journal of Lipid Research
DOI: 10.1194/jlr.M700478-JLR200
2008
Schinzel-Giedion syndrome: Report of splenopancreatic fusion and proposed diagnostic criteria
American Journal of Medical Genetics, Part A
DOI: 10.1002/ajmg.a.32277
2008
Phenotype-genotype characterization of alpha-thalassemia mental retardation syndrome due to isolated monosomy of 16p13.3
American Journal of Medical Genetics, Part A
DOI: 10.1002/ajmg.a.32056
2008
Mycophenolate mofetil and atherosclerosis: Results of animal and human studies
Annals of the New York Academy of Sciences
DOI: 10.1196/annals.1423.023
2007
Novel deletions of 14q11.2 associated with developmental delay, cognitive impairment and similar minor anomalies in three children
Journal of Medical Genetics
DOI: 10.1136/jmg.2007.050823
2007
Mycophenolate mofetil and animal models
Lupus
DOI: 10.1177/0961203306071675
2006
The beat goes on: ciliary proteins are defective in Meckel syndrome.
Clinical genetics
DOI: 10.1111/j.1399-0004.2006.00595b.x
2006
Oligonucleotide microarray analysis of genomic imbalance in children with mental retardation
American Journal of Human Genetics
DOI: 10.1086/507471
2006
Body weight is modulated by levels of full-length Huntingtin
Human Molecular Genetics
DOI: 10.1093/hmg/ddl072
2006
A new Marfan-like syndrome caused by pertubed transforming growth factor-ß signaling
Clinical Genetics
DOI: 10.1111/j.1399-0004.2005.0507c.x
2005
Another four bite the dust: mutations in a ubiquitously expressed filamin protein cause several skeletal dysplasias
Clinical Genetics
William T Gibson
DOI: 10.1111/j.1399-0004.2004.00295c.x
06/2004
So many asthma loci, so little time
Clinical Genetics
Paul C Orban and William T Gibson
DOI: 10.1111/j.1399-0004.2004.00295a.x
06/2004
Melanin-concentrating hormone receptor mutations and human obesity: Functional analysis
Obesity Research
2004
Mutational analysis of the serotonin receptor 5HT2c in severe early-onset human obesity
Canadian Journal of Physiology and Pharmacology
DOI: 10.1139/y04-025
2004
Melanin-concentrating hormone receptor mutations and human obesity: Functional analysis
Obesity Research
2004
Congenital leptin deficiency due to homozygosity for the ¿133G mutation: Report of another case and evaluation of response to four years of leptin therapy
Journal of Clinical Endocrinology and Metabolism
DOI: 10.1210/jc.2004-0376
2004
Searching for the 'natural': the case for the gene 'for' homosexuality.
Human reproduction and genetic ethics
2003
Contiguous deletion of the X-linked adrenoleukodystrophy gene (ABCD1) and DXS1357E: A novel neonatal phenotype dimilar to peroxisomal biogenesis disorders.
American Journal of Human Genetics
PubMed: 11992258
04/2002
Metabolism: Partial leptin deficiency and human adiposity
Nature
DOI: 10.1038/35102112
2001
First trimester fetal heart rate: Response to chorionic villus sampling in the chromosomally normal fetus
Fetal Diagnosis and Therapy
1997
The immunoglobulin heavy chain and disease association: application to pemphigus vulgaris
Human Genetics
DOI: 10.1007/BF00206963
1994
The immunoglobulin heavy chain and disease association: Application to pemphigus vulgaris
Human Genetics
1994
Susceptibility to multiple sclerosis is associated with the proximal immunoglobulin heavy chain variable region
Journal of Clinical Investigation
1991
Susceptibility to multiple sclerosis is associated with the proximal immunoglobulin heavy chain variable region
Journal of Clinical Investigation
1991
Current Projects
Our major interest is in rare mutations that predispose to common diseases, whether their effects are on aneurysm risk, food intake, energy expenditure or body growth (like the Weaver syndrome gene EZH2 and the Cohen-Gibson syndrome gene EED).
By studying rare human genetic disorders like Weaver syndrome, Cohen-Gibson syndrome, paired with data from animal models of obesity and leanness, we hope to derive valuable lessons that are relevant to common disease risk in the general population.
In addition to our recruitment of patients with rare overgrowth syndromes, we are also recruiting affected and unaffected members of families with Familial Brain Aneurysms.
CIHR Project Grant "Regulation of islet cell proliferation by p300" 2016-2019
NSERC Discovery Grant – 2011-2016
CIHR Project Grant "Functional Studies of Coding Variants in Polycomb Repressive Complex" 2020-2025
CIHR Project Grant "Insights from rare overgrowth syndromes for common diseases" 2016-2019
Heart and Stroke Foundation of Canada Grant-in-Aid "Next-Generation Sequencing for Rare, Highly-Penetrant Mutations in Familial Intracranial Aneurysms" 2017-2020
CIHR Clinician Scientist Phase 2 – 2006-2014
Promoted to Full Professor at UBC - 2018
CIHR Insititute of Genetics Clinician-Investigator Award - 2006-2008
Promoted to Associate Professor at UBC – 2013
Veronica Chow, Research Asst/Tech 3
Sharri Cyrus, Trainee
Daniel Gamu, Postdoctoral Research Fellow
Ru Chen Guo, Research Assistant
Kristine Louie
Michael Vermeulen, Graduate Research Asst
New research by Dr. William Gibson identifies multiple families with a gene defect that leads to a rare childhood overgrowth syndrome.
In a study recently published in Diabetes by Dr. Bill Gibson and UBC PhD student Chi Kin Wong, one patient’s rare mutation has led to the discovery of two proteins that help prevent diabetes from developing. Wong talks about how this research could lead to new treatments for diabetes and what rare diseases can teach us about how the human body works.
Human DNA testing could improve outcomes for patients with COVID-19.
That’s the key idea put forth in preliminary research posted this month to bioRxiv that highlights the potential benefits of testing COVID-19 patients for genetic variants of ACE2—the protein identified as the point-of-entry for the SARS-COV-2 virus into human cells.
We believe there’s nothing we can’t do with your support. It can take years to turn scientific breakthrough into new interventions and treatments. Funding helps speed the pace of change. When given the resources, we can bring transformative therapies – and hope – out of the laboratory and into the clinic to save and improve children’s lives.