Recurrent necrotizing cellulitis, multi-organ autoimmune disease and humoral immunodeficiency due to a novel NFKB1 frameshift mutation
| Autor: | Stephan Schreml, Christoph Brochhausen, Julia Schreml, Torsten E. Reichert, Ulrich Salzer, Tobias Ettl, Astrid Bergbreiter, Manfred Fliegauf, Yorick Söder, Teresa Jaeger, Andreas Redel, Antje Karle, Diane Bitzinger, Herbert Jägle, Reiner Neu, Mark Berneburg, Gerrit Spanier, Matthias Evert |
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| Rok vydání: | 2021 |
| Předmět: |
Male
0301 basic medicine Primary Immunodeficiency Diseases Pyoderma 030105 genetics & heredity Autoimmune Diseases Frameshift mutation 03 medical and health sciences Immune system Genetics Humans Medicine Frameshift Mutation Abscess Genetics (clinical) Immunodeficiency Autoimmune disease biology business.industry NF-kappa B p50 Subunit Cellulitis Syndrome General Medicine Middle Aged medicine.disease Pyoderma Gangrenosum 030104 developmental biology Immunology biology.protein Methotrexate Antibody business medicine.drug |
| Zdroj: | European Journal of Medical Genetics. 64:104144 |
| ISSN: | 1769-7212 |
| DOI: | 10.1016/j.ejmg.2021.104144 |
| Popis: | Background Mutations in NFKB1(nuclear factor of kappa light polypeptide gene enhancer in B-cells 1) are associated with a variety of clinical symptoms, including lymphadenopathy, splenomegaly, hepatomegaly, autoimmune haemolytic anaemia, arthralgia, recurrent respiratory tract infections and post-operative necrotizing cellulitis. Case presentation We describe a case of a 47-year-old man, who presented with deep necrotizing cellulitis after incision of a submucous abscess by a dentist. Surgical intervention led to a massive progress. Pyoderma gangraenosum (PG) was diagnosed clinically and confirmed histopathologically. High dose corticosteroids and intravenous immunoglobulins (IVIG) improved wound healing dramatically. Until now, immune mediated inflammation events not only affected the skin, but also multiple inner organs, i.e. the heart, lungs and gut. Sequencing of all coding exons of NFKB1 revealed a heterozygous 1bp deletion in exon 23 predicting a frameshift starting at codon Ala891 and resulting in a subsequent stop codon at position 6 in the new reading frame: NM_003998.4: c.2671del; p.(Ala891Glnfs*6) Acute episodes were always successfully treated with corticosteroids, IVIG and concomitant antibiotics. To prevent further exacerbations, the patient receives IVIG once a month, low-dose corticosteroids and methotrexate. Conclusion This is the first case of a patient with recurrent necrotizing cellulitis and immune mediated multi-organ involvement (heart, lungs, intestine) carrying the novel frameshift mutation c.2671del (p.Ala891Glnfs*6) in NFKB1 effectively treated with IVIG, low-dose corticosteroids and methotrexate. |
| Databáze: | OpenAIRE |
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