Development of a Population-Based Newborn Screening Method for Severe Combined Immunodeficiency in Manitoba, Canada

J Robert Thompson; Cheryl R Greenberg; Andrew Dick; Olga Jilkina; Luvinia Kwan; Tamar S Rubin; Teresa Zelinski; Marlis L Schroeder; Paul Van Caeseele

doi:10.3390/ijns4020019

Development of a Population-Based Newborn Screening Method for Severe Combined Immunodeficiency in Manitoba, Canada

Int J Neonatal Screen. 2018 Jun 19;4(2):19. doi: 10.3390/ijns4020019. eCollection 2018 Jun.

Authors

J Robert Thompson¹, Cheryl R Greenberg², Andrew Dick¹, Olga Jilkina³, Luvinia Kwan², Tamar S Rubin², Teresa Zelinski², Marlis L Schroeder², Paul Van Caeseele¹

Affiliations

¹ Cadham Provincial Laboratory, Winnipeg, MB R3E 3J7, Canada.
² Department of Pediatrics and Child Health, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, 546-715 McDermot Ave, Winnipeg, MB R3E 3R4, Canada.
³ CancerCare Manitoba, Winnipeg, MB R3E 0V9, Canada.

Abstract

The incidence of Severe Combined Immunodeficiency (SCID) in Manitoba, (1/15,000), is at least three to four times higher than the national average and that reported from other jurisdictions. It is overrepresented in two population groups: Mennonites (ZAP70 founder mutation) and First Nations of Northern Cree ancestry (IKBKB founder mutation). We have previously demonstrated that in these two populations the most widely utilized T-cell receptor excision circle (TREC) assay is an ineffective newborn screening test to detect SCID as these patients have normal numbers of mature T-cells. We have developed a semi-automated, closed tube, high resolution DNA melting procedure to simultaneously genotype both of these mutations from the same newborn blood spot DNA extract used for the TREC assay. Parallel analysis of all newborn screening specimens utilizing both TREC analysis and the high-resolution DNA procedure should provide as complete ascertainment as possible of SCID in the Manitoba population.

Keywords: SCID; TREC; newborn screening.