Alexandra F Freeman1, Joshua D Milner2. 1. National Institute of Allergy and Infectious Diseases, National Institutes of Health, NIH Building 10 Room 12C103, 9000 Rockville Pike, Bethesda, MD, 20892, USA. freemaal@mail.nih.gov. 2. Division of Allergy, Immunology and Rheumatology, Columbia University Medical Center, New York-Presbyterian Morgan Stanley Children's Hospital, New York, NY, USA.
Abstract
PURPOSE OF REVIEW: Over the last 13 years, the genetic etiologies have been determined for multiple conditions causing elevated serum IgE, infection susceptibilities, and variable other features. In this review, we discuss the clinical presentation, laboratory features, and genetics of these diseases caused by mutations in STAT3, DOCK8, PGM3, IL6ST, ZNF341, IL6R, IL6ST, CARD11, and CARD14, with particular focus given to STAT3LOF and DOCK8 deficiency. RECENT FINDINGS: Defining the phenotype of each of these syndromes with high IgE and infection susceptibility shows that some have a pronounced connective tissue phenotype such as STAT3LOF and IL6ST deficiency, some have worse viral susceptibility such as DOCK8 deficiency and heterozygous LOF CARD11, and some have more severe allergy and eczema such as LOF CARD14. Studying these distinct but overlapping monogenic diseases will allow a better understanding of more common disease processes such as allergy, eczema, infection susceptibility, scoliosis, and aneurysm.
PURPOSE OF REVIEW: Over the last 13 years, the genetic etiologies have been determined for multiple conditions causing elevated serum IgE, infection susceptibilities, and variable other features. In this review, we discuss the clinical presentation, laboratory features, and genetics of these diseases caused by mutations in STAT3, DOCK8, PGM3, IL6ST, ZNF341, IL6R, IL6ST, CARD11, and CARD14, with particular focus given to STAT3LOF and DOCK8 deficiency. RECENT FINDINGS: Defining the phenotype of each of these syndromes with high IgE and infection susceptibility shows that some have a pronounced connective tissue phenotype such as STAT3LOF and IL6ST deficiency, some have worse viral susceptibility such as DOCK8 deficiency and heterozygous LOF CARD11, and some have more severe allergy and eczema such as LOF CARD14. Studying these distinct but overlapping monogenic diseases will allow a better understanding of more common disease processes such as allergy, eczema, infection susceptibility, scoliosis, and aneurysm.
Authors: H Richard Droghini; J Pablo Abonia; Margaret H Collins; Joshua D Milner; Jonathan J Lyons; Alexandra F Freeman; Vincent A Mukkada; Kimberly A Risma; Marc E Rothenberg; Justin T Schwartz Journal: J Allergy Clin Immunol Pract Date: 2022-01-29