Our Research

Welcome to the Costain Lab! Our Lab uses advanced genetic technologies to facilitate diagnosis and discovery in children with suspected undiagnosed genetic diseases. Priority research populations include children with unexplained medical complexity and severe neurological impairment, and children with genetic or unexplained epilepsy. We are also pioneering new approaches for classifying and interpreting rare genetic variation, and working to support precision therapy development.

Selected Publications

For a complete list of Costain Lab publications, please visit PubMed.

  • Haque B*, Guirguis G*, Curtis M, Mohsin H, Walker S, Morrow MM, Costain G. A comparative medical genomics approach may facilitate the interpretation of rare missense variation. J Med Genet. 2024 Mar. doi:10.1136/jmg-2023- 109760. PMID: 38508706. 
  • Haque B, Cheerie D, Birkadze S, Xu AL, Nalpathamkalam T, Thiruvahindrapuram B, Walker S, Costain G. Estimating the proportion of nonsense variants undergoing the newly described phenomenon of manufactured splice rescue. Eur J Hum Genet. 2023 Nov. doi: 10.1038/s41431-023-01495-6. PMID: 38012313. 
  • D’Gama AM, Mulhern S, Sheidley BR, Boodhoo F, Buts S, Chandler NJ, Cobb J, Curtis M, Higginbotham EJ, Holland J, Khan T, Koh J, Liang NSY, McRae L, Nesbitt SE, Oby BT, Paternoster B, Patton A, Rose G, Scotchman E, Valentine R, Wiltrout KN; Gene-STEPS Study Group; IPCHiP Executive Committee; Hayeems RZ, Jain P, Lunke S, Marshall CR, Rockowitz S, Sebire NJ, Stark Z, White SM, Chitty LS, Cross JH, Scheffer IE, Chau V, Costain G, Poduri A, Howell KB, McTague A. Evaluation of the feasibility, diagnostic yield, and clinical utility of rapid genome sequencing in infantile epilepsy (Gene-STEPS): an international, multicentre, pilot cohort study. Lancet Neurol. 2023 Sep;22(9):812-825. doi: 10.1016/S1474-4422(23)00246-6. PMID: 37596007

  • Deshwar AR, Yuki KE, Hou H, Liang Y, Khan T, Celik A, Ramani A, Mendoza-Londono R, Marshall CR, Brudno M, Shlien A, Meyn MS, Hayeems RZ, McKinlay BJ, Klentrou P, Wilson MD, Kyriakopoulou L, Costain G, Dowling JJ. Trio RNA sequencing in a cohort of medically complex children. Am J Hum Genet. 2023 May 4;110(5):895-900. doi: 10.1016/j.ajhg.2023.03.006. Epub 2023 Mar 28.
    PMID: 36990084.

  • Haque B, Khan T, Ushcatz I, Curtis M, Pan A, Wu W, Orkin J, Costain G. Contemporary aetiologies of medical complexity in children: a cohort study. Arch Dis Child. 2023 Feb;108(2):147-149. doi: 10.1136/archdischild-2022-325094. Epub 2022 Dec 9. PMID: 36600318.

  • Scala M, Nishikawa M, Ito H, Tabata H, Khan T, Accogli A, Davids L, Ruiz A, Chiurazzi P, Cericola G, Schulte B, Monaghan KG, Begtrup A, Torella A, Pinelli M, Denommé-Pichon AS, Vitobello A, Racine C, Mancardi MM, Kiss C, Guerin A, Wu W, Gabau Vila E, Mak BC, Martinez-Agosto JA, Gorin MB, Duz B, Bayram Y, Carvalho CMB, Vengoechea JE, Chitayat D, Tan TY, Callewaert B, Kruse B, Bird LM, Faivre L, Zollino M, Biskup S; Undiagnosed Diseases Network; Telethon Undiagnosed Diseases Program; Striano P, Nigro V, Severino M, Capra V, Costain G, Nagata KI. Variant-specific changes in RAC3 function disrupt corticogenesis in neurodevelopmental phenotypes. Brain. 2022 Sep 14;145(9):3308-3327. doi: 10.1093/brain/awac106. PMID: 35851598 .

  • Pan A, Scodellaro S, Khan T, Ushcatz I, Wu W, Curtis M, Cohen E, Cohn RD, Hayeems RZ, Meyn MS, Orkin J, Otal J, Reuter MS, Walker S, Scherer SW, Marshall CR, Cohn I, Costain G. Pharmacogenetic profiling via genome sequencing in children with medical complexity. Pediatr Res. 2023 Mar;93(4):905-910. doi: 10.1038/s41390-022-02313-3. Epub 2022 Sep 27. PMID: 36167815.

  • Costain G, Liu Z, Mennella V, Radicioni G, Goczi AN, Albulescu A, Walker S, Ngan B, Manson D, Vali R, Khan M, Palaniyar N, Hill DB, Hall DA, Marshall CR, Knowles M, Zariwala MA, Kesimer M, Dell SD. Hereditary Mucin Deficiency Caused by Biallelic Loss of Function of MUC5B. Am J Respir Crit Care Med. 2022 Apr 1;205(7):761-768. doi: 10.1164/rccm.202106-1456OC. PMID: 35023825.

  • Costain G, Cohn RD, Scherer SW, Marshall CR. Genome sequencing as a diagnostic test. CMAJ. 2021 Oct 25;193(42):E1626-E1629. doi: 10.1503/cmaj.210549. PMID: 34697096; PMCID: PMC8562981.

  • Costain G, Walker S, Marano M, Veenma D, Snell M, Curtis M, Luca S, Buera J, Arje D, Reuter MS, Thiruvahindrapuram B, Trost B, Sung WWL, Yuen RKC, Chitayat D, Mendoza-Londono R, Stavropoulos DJ, Scherer SW, Marshall CR, Cohn RD, Cohen E, Orkin J, Meyn MS, Hayeems RZ. Genome Sequencing as a Diagnostic Test in Children With Unexplained Medical Complexity. JAMA Netw Open. 2020 Sep 1;3(9):e2018109. doi: 10.1001/jamanetworkopen.2020.18109. PMID: 32960281; PMCID: PMC7509619.

  • Costain G, Ghosh MC, Maio N, Carnevale A, Si YC, Rouault TA, Yoon G. Absence of iron-responsive element-binding protein 2 causes a novel neurodegenerative syndrome. Brain. 2019 May 1;142(5):1195-1202. doi: 10.1093/brain/awz072. PMID: 30915432; PMCID: PMC6487337.

  • Costain G, Callewaert B, Gabriel H, Tan TY, Walker S, Christodoulou J, Lazar T, Menten B, Orkin J, Sadedin S, Snell M, Vanlander A, Vergult S, White SM, Scherer SW, Hayeems RZ, Blaser S, Wodak SJ, Chitayat D, Marshall CR, Meyn MS. De novo missense variants in RAC3 cause a novel neurodevelopmental syndrome. Genet Med. 2019 Apr;21(4):1021-1026. doi: 10.1038/s41436-018-0323-y. Epub 2018 Oct 8. PMID: 30293988.

  • Costain G, Jobling R, Walker S, Reuter MS, Snell M, Bowdin S, Cohn RD, Dupuis L, Hewson S, Mercimek-Andrews S, Shuman C, Sondheimer N, Weksberg R, Yoon G, Meyn MS, Stavropoulos DJ, Scherer SW, Mendoza-Londono R, Marshall CR. Periodic reanalysis of whole-genome sequencing data enhances the diagnostic advantage over standard clinical genetic testing. Eur J Hum Genet. 2018 May;26(5):740-744. doi: 10.1038/s41431-018-0114-6. Epub 2018 Feb 16. PMID: 29453418; PMCID: PMC5945683.

  • Lionel AC, Costain G, Monfared N, Walker S, Reuter MS, Hosseini SM, Thiruvahindrapuram B, Merico D, Jobling R, Nalpathamkalam T, Pellecchia G, Sung WWL, Wang Z, Bikangaga P, Boelman C, Carter MT, Cordeiro D, Cytrynbaum C, Dell SD, Dhir P, Dowling JJ, Heon E, Hewson S, Hiraki L, Inbar-Feigenberg M, Klatt R, Kronick J, Laxer RM, Licht C, MacDonald H, Mercimek-Andrews S, Mendoza-Londono R, Piscione T, Schneider R, Schulze A, Silverman E, Siriwardena K, Snead OC, Sondheimer N, Sutherland J, Vincent A, Wasserman JD, Weksberg R, Shuman C, Carew C, Szego MJ, Hayeems RZ, Basran R, Stavropoulos DJ, Ray PN, Bowdin S, Meyn MS, Cohn RD, Scherer SW, Marshall CR. Improved diagnostic yield compared with targeted gene sequencing panels suggests a role for whole-genome sequencing as a first-tier genetic test. Genet Med. 2018 Apr;20(4):435-443. doi: 10.1038/gim.2017.119. Epub 2017 Aug 3. PMID: 28771251; PMCID: PMC5895460.

Funders

Our research would not be possible without the generous support of our funders!

Meet Our Team

Dr. Gregory Costain

Dr. Gregory Costain, MD, PhD

Dr. Costain is a physician-scientist who specializes in the diagnosis of rare genetic conditions in children. He joined the Division of Clinical and Metabolic Genetics at SickKids as a staff physician in 2020 after completing his residency training at the University of Toronto.

He runs the specialized Genetics of Epilepsy and severe Neurological Impairment Clinic (GENIC) at SickKids. He is also a Scientist-Track Investigator in the Genetics and Genome Biology program at SickKids Research Institute, and Assistant Professor at the University of Toronto.

His research program is focused on understanding the causes and consequences of rare variation in the human genome. His lab uses genome sequencing to discover new disease genes and genotype-phenotype associations, in a setting of an undiagnosed paediatric disease program.

Staff

Bushra Haque, MSc

Bioinformatician

Jashanpreet Sidhu

Clinical Research Coordinator

Aiyana Kaplan
Clinical Research Project Coordinator

Nicole Liang

Nicole Liang
Genetic Counsellor

Kaitlin Stanley
Genetic Counsellor

Amy Pan
Research Genetic Counsellor

Initials D and H

Denese Henry
Administrative Assistant

Students

David Cheerie

Graduate Student

Logan Newton

Graduate Student

Jimmy Nguyen

Graduate Student

Ziyi Dai

Graduate Student

Ivey Cao

Undergraduate Student

Rachel Stubits

Medical Student

Rachel Oh

Medical Genetics and Genomics Resident

Alumni

Sean Williams

Madeline Campbell

Ali Almail

George Guirguis

Jade Zhang

Jade Zhang

Tayyaba Khan

Tayyaba Khan

Meredith Curtis

Meredith Curtis

Alyssa Joynt

Alyssa Joynt

Wendy Wu

Wendy Wu

Collaborators

Anna Szuto

Anna Szuto
Genetic Counsellor

Contact Us

To contact the Costain Lab, fill out the form below!

PGCRL building entrance photo

Address

The Costain Lab
Genetics and Genome Biology Program
SickKids Research Institute
686 Bay Street
Toronto, ON, Canada
M5G 0A4