Estimated disease incidence of RAG1/2 mutations: A case report and querying the Exome Aggregation Consortium

Attila Kumánovics; Yu Nee Lee; Devin W Close; Emily M Coonrod; Boglarka Ujhazi; Karin Chen; Daniel G MacArthur; Gergely Krivan; Luigi D Notarangelo; Jolan E Walter

doi:10.1016/j.jaci.2016.07.027

Estimated disease incidence of RAG1/2 mutations: A case report and querying the Exome Aggregation Consortium

J Allergy Clin Immunol. 2017 Feb;139(2):690-692.e3. doi: 10.1016/j.jaci.2016.07.027. Epub 2016 Sep 5.

Authors

Affiliations

¹ Department of Pathology, University of Utah, Salt Lake City, Utah; ARUP Institute for Clinical and Experimental Pathology, ARUP Laboratories, Salt Lake City, Utah. Electronic address: [email protected].
² Division of Immunology, Children's Hospital, Harvard Medical School, Boston, Mass.
³ ARUP Institute for Clinical and Experimental Pathology, ARUP Laboratories, Salt Lake City, Utah.
⁴ Division of Allergy and Immunology, Massachusetts General Hospital for Children, Harvard Medical School, Boston, Mass.
⁵ Division of Allergy and Immunology, Department of Pediatrics, University of Utah, Salt Lake City, Utah.
⁶ Analytic and Translational Genetics Unit, Division of Allergy and Immunology, Massachusetts General Hospital for Children, Harvard Medical School, Boston, Mass.
⁷ United St Laszlo and St Istvan Hospital, Budapest, Hungary.
⁸ Division of Immunology, Children's Hospital, Harvard Medical School, Boston, Mass; Division of Allergy and Immunology, Massachusetts General Hospital for Children, Harvard Medical School, Boston, Mass. Electronic address: [email protected].

Abstract

RAG deficiency is emerging as one of the leading causes of SCID and leaky SCID with an estimated incidence of 1:336,000. Hypomorphic mutations in the RAG genes can also lead to highly variable delayed-onset combined immunodeficiency diseases. We estimate the population genetic frequency of these hypomorphic diseases as up to 1:181,000, suggesting that RAG1/2 mutations are likely to contribute to undiagnosed cases of combined immunodeficiencies.

Publication types

Case Reports
Letter
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

DNA-Binding Proteins / genetics*
DNA-Binding Proteins / immunology
Databases, Nucleic Acid*
Exome*
Female
Homeodomain Proteins / genetics*
Homeodomain Proteins / immunology
Humans
Incidence
Infant
Mutation*
Nuclear Proteins / genetics*
Nuclear Proteins / immunology
Severe Combined Immunodeficiency / epidemiology
Severe Combined Immunodeficiency / genetics*
Severe Combined Immunodeficiency / immunology

Substances

DNA-Binding Proteins
Homeodomain Proteins
Nuclear Proteins
RAG2 protein, human
RAG-1 protein

Abstract

Publication types

MeSH terms

Substances

Grants and funding