RNASEH2B Related Adult-Onset Interferonopathy
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To the Editor,
At least 18 different single-gene disorders have been described associated with elevated levels of type I interferon. These “type I interferonopathies” typically result in severe pediatric disorders, including STING-associated vasculopathy of infancy (SAVI) caused by gain of function mutations in TMEM173, spondyloenchondropdysplasia (SPENCD) caused by biallelic ACP5 mutations, and Aicardi-Goutières syndrome (AGS) caused by mutations in one of seven different genes: TREX1, RNASEH2A, RNASEH2B, RNASEH2C, ADAR1, SAMHD1, or IFIH1 . AGS is the most commonly recognized interferonopathy and in over 90% of cases presents within the first year of life with neurological impairment associated with intracranial calcification and leukodystrophy, and in around a third of cases acral chilblains develop . The type I interferonopathies occur due to aberrant metabolism of nucleic acids/dysregulation of the interferon pathway, resulting in induction of type I interferon and...
This report presents independent research funded by the National Institute for Health Research (NIHR) (NIHR Transitional Research Fellowship, Dr. Tracy Briggs, TRF-2016-09-002) and supported by the NIHR Manchester Biomedical Research Centre.
Compliance with Ethical Standards
With research consent (REC reference 17/SC/0026). The views expressed are those of the authors and not necessarily those of the NHS, the NIHR, or the Department of Health.
Type I interferonopathies, including RNASEH2B mutations, should be considered in adults with severe digital ischemia.
Conflict of Interest
The authors declare that they have no conflict of interest.
- 7.Bursztejn AC, Briggs TA, del Toro Duany Y, Anderson BH, O'Sullivan J, Williams SG, et al. Unusual cutaneous features associated with a heterozygous gain-of-function mutation in IFIH1: overlap between Aicardi-Goutières and Singleton-Merten syndromes. Br J Dermatol. 2015;173(6):1505–13.CrossRefGoogle Scholar