Our recent publications - highlights


Haploinsufficiency of vascular endothelial growth factor related signaling genes is associated with tetralogy of Fallot
Reuter MS, Jobling R, Chaturvedi RR, Manshaei R, Costain G, Heung T, Curtis M, Hosseini SM, Liston E, Lowther C, Oechslin E, Sticht H, Thiruvahindrapuram B, Mil SV, Wald RM, Walker S, Marshall CR, Silversides CK, Scherer SW, Kim RH, Bassett AS.
Genet Med. 2019 Apr;21(4):1001-1007. Epub 2018 Sep 20.
doi: 10.1038/s41436-018-0260-9.

  • see the UHN Newsroom article

  • The authors discovered that some patients with tetralogy of Fallot carry variants in the VEGF pathway genes, which code for proteins important in blood vessel and heart development. The variants include ones that changes the protein sequence and are expected to cause the protein to malfunction, as well as those that lead to partly-deleted protein. This research supports the idea that changes the VEGF pathway genes are involved in the formation of tetralogy of Fallot.

[Return to top]


Neurocognition and adaptive functioning in a genetic high risk model of schizophrenia
Fiksinski AM, Breetvelt EJ, Lee YJ, Boot E, Butcher N, Palmer L, Chow EWC, Kahn RS, Vorstman JAS, Bassett AS.
Psychol Med. 2018 Aug 1:1-8. [Epub ahead of print]
doi: 10.1017/S0033291718001824.

  • In this study the authors investigated specific areas of neurocognition in 99 adults with 22q, identified areas of relative strengths and weaknesses, and found that the better one’s functioning in certain skills (called Executive Performance), which could potentially be improved through cognitive interventions, the better one’s daily-life functioning as an adult. These results may help caregivers and clinicians to recognize the relative strengths and weaknesses in learning of people with 22q.

Neuropsychiatric expression and catatonia in 22q11.2 deletion syndrome: an overview and case series
Butcher NJ, Boot E, Lang AE, Andrade D, Vorstman JA, Bassett AS
American Journal of Medical Genetics A (pages 1-14), 2018, e-published 19 May 2018

  • Catatonia is a set of symptoms that include abnormal involuntary movements and behaviours that sometimes occur in individuals with psychiatric conditions like schizophrenia and depression and in some neurological diseases. In this study, the authors provide an overview of the psychiatric and neurological symptoms and conditions associated with catatonia in adults with 22q. The results may help with the diagnosis of catatonia so that effective treatment can be provided as early as possible.

Elucidating the diagnostic odyssey of 22q11.2 deletion syndrome
Palmer LD, Butcher NJ, Boot E, Hodgkinson KA, Heung T, Chow EWC, Guna A, Crowley TB, Zackai E, McDonald-McGinn DM, Bassett AS
American Journal of Medical Genetics A 176:936-944, 2018
doi: 10.1002/ajmga.38645

  • Individuals with 22q are often undiagnosed for years because this condition is not easily recognizable. This study analyzed the time it took for a diagnosis of 22q and reasons for delays across age and groups in Toronto and Philadelphia. Problems with the palate and heart were associated with shorter times to a 22q diagnosis. Non-European ancestry lead to longer times. There is a great need for education about 22q so that the condition is more widely known.

[Return to top]


Rare Genome-Wide Copy Number Variation and Expression of Schizophrenia in 22q11.2 Deletion Syndrome.
Bassett AS, Lowther C, Merico D, Costain G, Chow EWC, van Amelsvoort T, McDonald-McGinn D, Gur RE, Swillen A, Van den Bree M, Murphy K, Gothelf D, Bearden CE, Eliez S, Kates W, Philip N, Sashi V, Campbell L, Vorstman J, Cubells J, Repetto GM, Simon T, Boot E, Heung T, Evers R, Vingerhoets C, van Duin E, Zackai E, Vergaelen E, Devriendt K, Vermeesch JR, Owen M, Murphy C, Michaelovosky E, Kushan L, Schneider M, Fremont W, Busa T, Hooper S, McCabe K, Duijff S, Isaev K, Pellecchia G, Wei J, Gazzellone MJ, Scherer SW, Emanuel BS, Guo T, Morrow BE, Marshall CR; International 22q11.2DS Brain and Behavior Consortium. Am J Psychiatry. 2017 Nov 1;174(11):1054-1063. doi: 10.1176/appi.ajp.2017.16121417. Epub 2017 Jul 28.

  • The authors found that rare copy number variants (CNVs) that overlap protein-coding sequences can contribute to an increased risk of schizophrenia in individuals with 22q11.2 deletions. These CNVs include both rare duplications that overlap genes involved in neuronal function, as well as rare deletions that overlap more genes in individuals who develop schizophrenia.

Genome-Wide Association Study to Find Modifiers for Tetralogy of Fallot in the 22q11.2 Deletion Syndrome Identifies Variants in the GPR98 Locus on 5q14.3.
Guo T, Repetto GM, McDonald McGinn DM, Chung JH, Nomaru H, Campbell CL, Blonska A, Bassett AS, Chow EWC, Mlynarski EE, Swillen A, Vermeesch J, Devriendt K, Gothelf D, Carmel M, Michaelovsky E, Schneider M, Eliez S, Antonarakis SE, Coleman K, Tomita-Mitchell A, Mitchell ME, Digilio MC, Dallapiccola B, Marino B, Philip N, Busa T, Kushan-Wells L, Bearden CE, Piotrowicz M, Hawuła W, Roberts AE, Tassone F, Simon TJ, van Duin EDA, van Amelsvoort TA, Kates WR, Zackai E, Johnston HR, Cutler DJ, Agopian AJ, Goldmuntz E, Mitchell LE, Wang T, Emanuel BS, Morrow BE; International 22q11.2 Consortium/Brain and Behavior Consortium. Circ Cardiovasc Genet. 2017 Oct;10(5). pii: e001690. doi: 10.1161/CIRCGENETICS.116.001690.

  • The authors performed a genome-wide association study to search for variants associated with tetralogy of Fallot (TOF) in individuals with 22q. They found that TOF was signifcantly associated with a single-nucleotide polymorphism (SNP) in an intron of GPR98, which codes for G-protein-coupled receptor V1), on chromosome 5q14.3.

22q11.2 deletion syndrome lowers seizure threshold in adult patients without epilepsy.

Wither RG, Borlot F, MacDonald A, Butcher NJ, Chow EWC, Bassett AS, Andrade DM. Epilepsia. 2017 Jun;58(6):1095-1101. doi: 10.1111/epi.13748. Epub 2017 Apr 27.

  • This research shows that the prevalence of epilepsy and acute symptomatic seizures in adults with 22q11.2DS is higher than that of the general population. Although hypocalcemia is a risk factor, the main cause of seizures in adults with 22q11.2DS is their exposure to antipsychotics and antidepressants.

Autism spectrum and psychosis risk in the 22q11.2 deletion syndrome. Findings from a prospective longitudinal study

Fiksinski AM, Breetvelt EJ, Duijff SN, Bassett AS, Kahn RS, Vorstman JA: Schizophr Res. 2017 Jan 21. pii: S0920-9964(17)30044-0. doi: 10.1016/j.schres.2017.01.032. [Epub ahead of print]

  • This research investigated whether Autism Spectrum Disorders (ASDs) in individuals with 22q are actually associated with an increased risk for development of schizophrenia, or whether psychotic disorders and ASDs may arise independently. The answer was that they are independent conditions.

Neuroimaging and clinical features in adults with a 22q11.2 deletion at risk of Parkinson's disease

Butcher NJ, Marras C, Pondal M, Rusjan P, Boot E, Christopher L, Repetto GM, Fritsch R, Chow EW, Masellis M, Strafella AP, Lang AE, Bassett AS. Brain (2017) Mar 24. (doi: 10.1093/brain/awx053)

  • See the UHN Research News article

  • This research explored signs and symptoms in adults with 22q11.2 deletion syndrome that may be related to a risk of developing Parkinson's disease, a treatable movement disorder that affect some older adults. By using a combination of clinical assessments and brain imaging, we found new evidence that adults with 22q11.2 deletion syndrome may have problems with movements and may also have differences in dopamine, a brain chemical that can affect the way we move and feel. These results may help us better understand conditions that affect adults with 22q11.2DS, such as Parkinson's disease and schizophrenia.

Obesity in adults with 22q11.2 deletion syndrome
Voll SL, Boot E, Butcher NJ, Cooper S, Heung T, Chow EW, Silversides CK, Bassett AS: Genet Med. 19(2):204-208, 2017. (doi: 10.1038/gim.2016.98)

  • This study compared the heights and weights of adults with 22q to the Canadian population. Starting in the 19-24 age group, on average people with 22q had higher rates of obesity whether they were or were not taking medications that can increase the risk for weight gain.

[Return to top]


The importance of copy number variation in congenital heart disease
Costain G, Silversides CK, Bassett AS.
Genomic Medicine (2016) 1, 16031; (doi:10.1038/npjgenmed.2016.31); published online 14 September 2016

  • This review article looked at the contribution of genome-wide rare copy number variation (CNV) to congenital heart disease (CHD). Prevalence of CHD in people with CNV was discussed, as well as clinical and research advances paving the way for whole-genome sequencing to understand the genetic basis for CHD in the future.

Internet Safety Issues for Adolescents and Adults with Intellectual Disabilities.
Buijs PC, Boot E, Shugar A, Fung WL, Bassett AS.
J Appl Res Intellect Disabil. 2016 Feb 23. (doi: 10.1111/jar.12250). [Epub ahead of print]

  • This brief report looked at some potential challenges of internet safety for adolescents and adults with 22q. Examples of particular dangers were presented, and safety interventions and next steps for doctors and clinicians were discussed.

[Return to top]


22q11.2 deletion syndrome
McDonald-McGinn DM, Sullivan KE, Marino B, Philip N, Swillen A, Vorstman JA, Zackai EH, Emanuel BS, Vermeesch JR, Morrow BE, Scambler PJ, Bassett AS. (2015) Nature Reviews Disease Primers 1:15071. doi: 10.1038/nrdp.2015.71.

Response to clozapine in a clinically identifiable subtype of schizophrenia: 22q11.2 deletions mediate side effect risk and dosage.

Butcher NJ, Fung WLA, Fitzpatrick L, Guna A, Andrade D, Lang A, Chow EWC, Bassett AS: British Journal of Psychiatry 206:484-491, 2015 (doi:10.1192/bjp.bp.114.151837)

  • This research explored how individuals with 22q and schizophrenia respond to the medication clozapine, and how it differs from individuals with schizophrenia who do not have 22q. We found that a lower dose of clozapine and using preventative measures can help lower the risks of side effects for individuals with 22q.

Movement disorders and other motor abnormalities in adults with 22q11.2 deletion syndrome

Boot E, Butcher NJ, van Amelsvoort TAMJ, Lang AE, Marras C, Pondal M, Andrade DM, Fung WLA, Bassett AS: American Journal of Medical Genetics Part A 167:639-645, 2015 (doi:10.1002/ajmg.a.36928)

  • This research looked at five examples of adults with 22q who also had movement disorders, which could range from balance problems to shakiness. Through these examples, we were able to suggest common symptoms and possible causes of these disorders, which can help other health care professionals to provide better care for individuals with 22q.

Practical guidelines for managing adults with 22q11.2 deletion syndrome.

Fung WLA, Butcher NJ, Costain G, Andrade DM, Boot E, Chow EWC, Chung B, Cytrynbaum C, Faghfoury H, Fishman L, García-Miñaúr r S, George SR, Lang AE, Repetto G, Shugar A, Silversides C, Swillen A, van Amelsvoort T, McDonald-McGinn DM, Bassett AS and the International 22q11.2DS Consortium: Genetics in Medicine 17:599-609, 2015 (doi:10.1038/gim.2014.175)

  • This review is a practice guideline for providing health care to adults with 22q. An international panel of researchers collaborated to contribute to this paper, with topics covering the management of psychiatric and medical conditions, as well as how to identify these conditions in adults with 22q.

[Return to top]


Prevalence of hypocalcaemia and its associated features in 22q11.2 deletion syndrome

Cheung ENM, George SR, Costain GA, Andrade DM, Chow EWC, Silversides CK, Bassett AS: Clinical Endocrinology 81:190-196, 2014 (doi: 10.1111/cen.12466)

  • This research explored how common low calcium levels are in individuals with 22q, and what the possible causes are. We found that in addition to changes in parathyroid function, low thyroid function may also play a role in causing low calcium levels. Also, individuals with 22q can have low levels of magnesium, which can further lower calcium. Dietary intake such as pop and alcohol were also found to lower calcium levels, and reducing intake of these drinks is an important preventative strategy.

[Return to top]