Understanding of Severe Combined Immunodeficiency and Carrier Status in the U.S.-Based Irish Traveller Population

Abstract

IntroductionThe Irish Travellers are an ethnically distinct minority community originating from Ireland, with substantial immigration to the U. S. resulting in a current subpopulation estimated around 20,000. Given the history of cultural endogamy in this community, there are known increased rates of severe combined immunodeficiency (SCID), with two recombinase activating gene 1 pathogenic variants (RAG1; p.Arg897*and p.Ser259Alafs*5) and one novel non-homologous end-joining 1 gene variant (NHEJ1; p.Gln224Argfs*27) detected in the US community. However, knowledge of rare genetic disorders, including how they are passed and the value of carrier testing, is limited among some members of this population. MethodsA multi-institutional collaboration developed an outreach project for SCID patients and their relatives in the U.S.-based Irish Traveller community. SCID patients were identified through newborn screening and pedigree interviews. Genetic testing for SCID variants was offered to kindred members, prioritizing members of child-bearing age. An online educational program was designed to identify knowledge gaps and disseminate information on SCID and implications of carrier status. Results and DiscussionBaseline knowledge and attitude assessments prior to educational intervention were obtained from 28 kindred members, all of whom were female and the majority (n = 23) were of child bearing age. Similar to their counterparts in Ireland, the majority (n = 21) had less than a high school diploma. 12 respondents identified three or more family members diagnosed with SCID. The majority of respondents (n ≥17) strongly agreed on the importance of knowing what diseases run in their family. However, only a minority (n ≤8) were able to correctly identify how autosomal dominant, autosomal recessive, and X-linked diseases were passed down. Open ended discussions with key members of this kindred also helped identify religious and cultural barriers which contributed to hesitancy around genetic testing in this underserved community. Early diagnosis of affected members, enabled by educational sessions and carrier screening within this high-risk population, is vital to increase preparedness for the birth of a child with SCID. This is especially important in the case of SCID caused by NHEJ1, as the radiosensitivity caused by this mutation necessitates treatment and conditioning protocols which differ from that of SCID caused by RAG1 mutations.