Genotyping an immunodeficiency causing c.1624–11G>A ZAP70 mutation in Canadian Mennonites

BMC Medical Genetics

Research Article

M. L. Schroeder¹  T. Zelinski²  B. Triggs-Raine² 

[1] Department of Pediatrics and Child Health, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada;Department of Pediatrics and Child Health, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada;Department of Biochemistry and Medical Genetics, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada;

关键词: Affected Individual;    Primary Immunodeficiency;    Severe Combine Immunodeficiency;    Buccal Swab;    Random Individual;   

DOI  :  10.1186/s12881-016-0312-4

 received in 2015-10-31, accepted in 2016-06-10,  发布年份 2016

来源: Springer

【 摘 要 】

BackgroundPrimary immunodeficiency is a life-threatening genetic disease that appeared to have an increased incidence in Manitoba Mennonites. Determining the genetic basis of this immunodeficiency was an essential step for providing early and appropriate medical intervention.MethodsInitially, DNA from probands affected with primary immunodeficiency and their family members was assessed for linkage to genes previously associated with immunodeficiency. Candidate genes were sequenced to identify the causative mutation. The frequency of the mutation among first and second degree relatives, as well as apparently unrelated community members was analyzed using a PCR-based assay.ResultsA previously described c.1624–11G>A mutation in ZAP70 was identified as the causative mutation in all affected probands that were analyzed. Among 125 study participants of Mennonite descent, 79 genotyped as normal, 39 were carriers and seven were affected. None of 115 non-Mennonite random individuals carried the mutation, whereas one of ten random DNA samples from individuals who self-identified as Mennonite was a carrier.ConclusionsIn collaboration with the target community, we have developed a robust screening test for determining ZAP70 genotype. Early identification of affected individuals has provided an opportunity for timely clinical intervention, while carrier identification has allowed for genetic counselling of at risk couples.

【 授权许可】

CC BY   
© The Author(s). 2016