Details

Autor(en) / Beteiligte

• Kumánovics, Attila, MD
• Lee, Yu Nee, PhD
• Close, Devin W., PhD
• Coonrod, Emily M., PhD
• Ujhazi, Boglarka, MSc
• Chen, Karin, MD
• MacArthur, Daniel G., PhD
• Krivan, Gergely, MD
• Notarangelo, Luigi D., MD
• Walter, Jolan E., MD, PhD

Titel

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

Ist Teil von

• Journal of allergy and clinical immunology, 2017-02, Vol.139 (2), p.690-692.e3

Ort / Verlag

United States: Elsevier Limited

Erscheinungsjahr

2017

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• To the Editor: There is a great diversity of RAG1- and RAG2-dependent primary immunodeficiencies ranging from severe combined immunodeficiency (SCID) to various late-onset combined immunodeficiencies, as complete lack of RAG activity leads to absence of mature B and T cells (T-B- SCID), whereas hypomorphic RAG mutations allow limited generation of T and or B cells, resulting in various clinical phenotypes distinct from SCID.1,2 Currently, there are no peripheral blood-based functional assays for the evaluation of RAG activity. [...]the pathogenicity of RAG variants is determined using prediction programs and in vitro V(D)J recombination assays.3 Critical to this evaluation is the population frequency of the variants. The number of individuals who are homozygous or compound heterozygous for decreased-function RAG variants is about 9.68 x 10-7 or approximately 1 in 1,000,000. Because this estimation is substantially lower than the frequency of RAG1/2 mutations observed by newborn screening (1 in 336,000),E4 we conclude that the ExAC database currently underestimates the frequency of RAG1/2 deficiency diseases, and the number of individuals who are homozygous or compound heterozygous for decreased-function RAG variants is estimated to be between 1 in 181,000 and 1 in 336,000.