Paternal gonadal mosaicism as cause of a puzzling inheritance pattern of activated PI3-kinase delta syndrome

Abstract

Birth defects caused by de novo chromosomal abnormalities resulting in single-gene defects occur in approximately 5% of all live births. [1] Wyrobek A.J. Mulvihill J.J. Wassom J.S. et al. Assessing human germ-cell mutagenesis in the postgenome era: a celebration of the legacy of William Lawson (Bill) Russell. Environ Mol Mutagen. 2007; 48: 71-95 Crossref PubMed Scopus (48) Google Scholar Affected offspring have a broad range of illnesses, including primary immunodeficiency diseases, a genetically heterogeneous group of disorders presenting with a clinical spectrum of mild to severe infections, often complicated by autoimmunity and malignancies. [2] Picard C. Al-Herz W. Bousfiha A. et al. Primary immunodeficiency diseases: an update on the classification from the International Union of Immunological Societies Expert Committee for Primary Immunodeficiency 2015. J Clin Immunol. 2015; 35: 696-726 Crossref PubMed Scopus (517) Google Scholar Most primary immunodeficiency diseases are monogenic diseases with a Mendelian inheritance pattern. [2] Picard C. Al-Herz W. Bousfiha A. et al. Primary immunodeficiency diseases: an update on the classification from the International Union of Immunological Societies Expert Committee for Primary Immunodeficiency 2015. J Clin Immunol. 2015; 35: 696-726 Crossref PubMed Scopus (517) Google Scholar