Health Conditions Related to Genetic Changes
Bare lymphocyte syndrome type II
At least seven mutations in the RFXAP gene have been found to cause an immune system disorder called bare lymphocyte syndrome type II (BLS II). BLS II is a type of combined immunodeficiency (CID), in which affected individuals have virtually no immune protection from foreign invaders. Consequently, individuals with BLS II have persistent infections in the respiratory, gastrointestinal, and urinary tracts, which can be life-threatening.
Mutations in the RFXAP gene lead to production of an abnormally short RFXAP protein that likely does not function properly, if any protein is produced at all. These changes impair binding of the RFX complex to DNA, which prevents transcription of MHC class II proteins. Consequently, lymphocytes lack any MHC class II proteins on their surface, and the body has difficulty getting rid of bacteria, viruses, and fungi, leading to the persistent infections characteristic of BLS II.
More About This Health ConditionOther disorders
At least one mutation in the RFXAP gene has been found to cause bare lymphocyte syndrome type III (BLS III). This type of bare lymphocyte syndrome is characterized by absence of MHC class II proteins and a reduced amount of MHC class I proteins on the surface of lymphocytes. However, it is unclear if BLS III is a distinct diagnosis. Some doctors consider such cases to be BLS II (described above). Both types of BLS cause persistent, life-threatening infections.
The RFXAP gene mutation involved in BLS III likely impairs the function of the RFX complex, preventing transcription of MHC class II genes and reducing the activity of MHC class I genes. Without the important immune system proteins produced from these genes, the body is less able to fight infections. It is unclear why certain RFXAP gene mutations impair production of MHC class I proteins and others do not.
Other Names for This Gene
- regulatory factor X-associated protein
- RFX DNA-binding complex 36 kDa subunit
- RFX-associated protein
Additional Information & Resources
Tests Listed in the Genetic Testing Registry
Scientific Articles on PubMed
Catalog of Genes and Diseases from OMIM
References
- Briggs L, Laird K, Boss JM, Garvie CW. Formation of the RFX gene regulatory complex induces folding of the interaction domain of RFXAP. Proteins. 2009 Aug 15;76(3):655-64. doi: 10.1002/prot.22379. Citation on PubMed or Free article on PubMed Central
- Burd AL, Ingraham RH, Goldrick SE, Kroe RR, Crute JJ, Grygon CA. Assembly of major histocompatibility complex (MHC) class II transcription factors: association and promoter recognition of RFX proteins. Biochemistry. 2004 Oct 12;43(40):12750-60. doi: 10.1021/bi030262o. Citation on PubMed
- Garvie CW, Boss JM. Assembly of the RFX complex on the MHCII promoter: role of RFXAP and RFXB in relieving autoinhibition of RFX5. Biochim Biophys Acta. 2008 Dec;1779(12):797-804. doi: 10.1016/j.bbagrm.2008.07.012. Epub 2008 Aug 6. Citation on PubMed
- Gobin SJ, Peijnenburg A, van Eggermond M, van Zutphen M, van den Berg R, van den Elsen PJ. The RFX complex is crucial for the constitutive and CIITA-mediated transactivation of MHC class I and beta2-microglobulin genes. Immunity. 1998 Oct;9(4):531-41. doi: 10.1016/s1074-7613(00)80636-6. Citation on PubMed
- Gokturk B, Artac H, van Eggermond MJ, van den Elsen P, Reisli I. Type III bare lymphocyte syndrome associated with a novel RFXAP mutation: a case report. Int J Immunogenet. 2012 Aug;39(4):362-4. doi: 10.1111/j.1744-313X.2012.01105.x. Epub 2012 Mar 6. Citation on PubMed
- Villard J, Lisowska-Grospierre B, van den Elsen P, Fischer A, Reith W, Mach B. Mutation of RFXAP, a regulator of MHC class II genes, in primary MHC class II deficiency. N Engl J Med. 1997 Sep 11;337(11):748-53. doi: 10.1056/NEJM199709113371104. Citation on PubMed
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