TY - JOUR
T1 - Somatic mosaicism in inborn errors of immunity
T2 - Current knowledge, challenges, and future perspectives
AU - Aluri, Jahnavi
AU - Cooper, Megan A.
N1 - Publisher Copyright:
© 2023 Elsevier Ltd
PY - 2023/5
Y1 - 2023/5
N2 - Inborn errors of immunity (IEI) are a diverse group of monogenic disorders of the immune system due to germline variants in genes important for the immune response. Over the past decade there has been increasing recognition that acquired somatic variants present in a subset of cells can also lead to immune disorders or ‘phenocopies’ of IEI. Discovery of somatic mosaicism causing IEI has largely arisen from investigation of seemingly sporadic cases of IEI with predominant symptoms of autoinflammation and/or autoimmunity in which germline disease-causing variants are not detected. Disease-causing somatic mosaicism has been identified in genes that also cause germline IEI, such as FAS, and in genes without significant corresponding germline disease, such as UBA1 and TLR8. There are challenges in detecting low-level somatic variants, and it is likely that the extent of the somatic mosaicism causing IEI is largely uncharted. Here we review the field of somatic mosaicism leading to IEI and discuss challenges and methods for somatic variant detection, including diagnostic approaches for molecular diagnoses of patients.
AB - Inborn errors of immunity (IEI) are a diverse group of monogenic disorders of the immune system due to germline variants in genes important for the immune response. Over the past decade there has been increasing recognition that acquired somatic variants present in a subset of cells can also lead to immune disorders or ‘phenocopies’ of IEI. Discovery of somatic mosaicism causing IEI has largely arisen from investigation of seemingly sporadic cases of IEI with predominant symptoms of autoinflammation and/or autoimmunity in which germline disease-causing variants are not detected. Disease-causing somatic mosaicism has been identified in genes that also cause germline IEI, such as FAS, and in genes without significant corresponding germline disease, such as UBA1 and TLR8. There are challenges in detecting low-level somatic variants, and it is likely that the extent of the somatic mosaicism causing IEI is largely uncharted. Here we review the field of somatic mosaicism leading to IEI and discuss challenges and methods for somatic variant detection, including diagnostic approaches for molecular diagnoses of patients.
KW - Genetics
KW - Immunity
KW - Inborn errors of immunity
KW - Mosaicism
KW - Next-generation sequencing
KW - Primary immunodeficiency
KW - Somatic
UR - http://www.scopus.com/inward/record.url?scp=85152726438&partnerID=8YFLogxK
U2 - 10.1016/j.smim.2023.101761
DO - 10.1016/j.smim.2023.101761
M3 - Review article
C2 - 37062181
AN - SCOPUS:85152726438
SN - 1044-5323
VL - 67
JO - Seminars in immunology
JF - Seminars in immunology
M1 - 101761
ER -