Prenatal diagnosis and carrier detection for Athabascan severe combined immunodeficiency disease

Objectives: Severe combined immunodeficiency disease occurs at a high incidence among Athabascan-speaking Navajo and Apache children (SCIDA). We linked the SCIDA gene to chromosome 10p and recently identified a common nonsense mutation in Artemis/SCIDA. In this study we compared polymorphic markers linked to SCIDA and the point mutation which creates an NspI site on exon 8 for prenatal diagnosis and carrier detection. Methods: We tested five amniocentesis samples, two cord blood and two blood samples from eight at-risk families using polymorphic DNA markers tightly linked to SCIDA. We amplified the region of exon 8 of Artemis/SCIDA and evaluated the products for the NspI site in each sample plus samples from 30 unrelated healthy Navajos. Results: We correctly predicted that three were affected and six were unaffected. Two of the unaffected appear to be carriers based on our haplotype analysis. Retrospective analysis for the gene mutation confirmed the DNA analysis. Finally, 10% of the normal Navajo controls were carriers. Conclusions: We demonstrate the feasibility of prenatal diagnosis and carrier detection for SCIDA in the families at risk as well as the availability of a rapid screening test for the SCIDA founder mutation that can be used in all Navajo and Apache newborns and at-risk fetuses.