Incomplete penetrance in primary immunodeficiency: a skeleton in the closet.

摘要: Primary immunodeficiencies (PIDs) comprise a diverse group of over 400 genetic disorders that result in clinically apparent immune dysfunction. Although PIDs are classically considered as Mendelian with complete penetrance, we now understand absent or partial clinical disease is often noted individuals harboring disease-causing genotypes. Despite the frequency incomplete penetrance PID, no conceptual framework exists to categorize and explain these occurrences. Here, by reviewing decades reports on PID identify four recurrent themes namely genotype quality, (epi)genetic modification, environmental influence, mosaicism. For each principles, review what known, underscore remains unknown, propose future experimental approaches fill gaps our understanding. content herein relates specifically inborn errors immunity, concepts generalizable across diseases.