Cutaneous Vasculitis and Digital Ischaemia Caused by Heterozygous Gain-of-Function Mutation in C3
It is now increasingly recognized that some monogenic autoinflammatory diseases and immunodeficiencies cause vasculitis, although genetic causes of vasculitis are extremely rare. We describe a child of non-consanguineous parents who presented with cutaneous vasculitis, digital ischaemia and hypocomp...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2018-11-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fimmu.2018.02524/full |
| _version_ | 1818266029156990976 |
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| author | Ebun Omoyinmi Ebun Omoyinmi Iman Mohamoud Kimberly Gilmour Paul A. Brogan Paul A. Brogan Despina Eleftheriou Despina Eleftheriou Despina Eleftheriou |
| author_facet | Ebun Omoyinmi Ebun Omoyinmi Iman Mohamoud Kimberly Gilmour Paul A. Brogan Paul A. Brogan Despina Eleftheriou Despina Eleftheriou Despina Eleftheriou |
| author_sort | Ebun Omoyinmi |
| collection | DOAJ |
| description | It is now increasingly recognized that some monogenic autoinflammatory diseases and immunodeficiencies cause vasculitis, although genetic causes of vasculitis are extremely rare. We describe a child of non-consanguineous parents who presented with cutaneous vasculitis, digital ischaemia and hypocomplementaemia. A heterozygous p.R1042G gain-of-function mutation (GOF) in the complement component C3 gene was identified as the cause, resulting in secondary C3 consumption and complete absence of alternative complement pathway activity, decreased classical complement activity, and low levels of serum C3 with normal C4 levels. The same heterozygous mutation and immunological defects were also identified in another symptomatic sibling and his father. C3 deficiency due GOF C3 mutations is thus now added to the growing list of monogenic causes of vasculitis and should always be considered in vasculitis patients found to have persistently low levels of C3 with normal C4. |
| first_indexed | 2024-12-12T20:00:12Z |
| format | Article |
| id | doaj.art-59cb6869aca94d9abb422e0be96df7e6 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-12T20:00:12Z |
| publishDate | 2018-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-59cb6869aca94d9abb422e0be96df7e62022-12-22T00:13:47ZengFrontiers Media S.A.Frontiers in Immunology1664-32242018-11-01910.3389/fimmu.2018.02524420552Cutaneous Vasculitis and Digital Ischaemia Caused by Heterozygous Gain-of-Function Mutation in C3Ebun Omoyinmi0Ebun Omoyinmi1Iman Mohamoud2Kimberly Gilmour3Paul A. Brogan4Paul A. Brogan5Despina Eleftheriou6Despina Eleftheriou7Despina Eleftheriou8Infection, Inflammation and Rheumatology Section, UCL Great Ormond Street Institute of Child Health, London, United KingdomGreat Ormond Street Hospital NHS Foundation Trust, London, United KingdomInfection, Inflammation and Rheumatology Section, UCL Great Ormond Street Institute of Child Health, London, United KingdomClinical Immunology Laboratory, Great Ormond Street Hospital NHS Foundation Trust, London, United KingdomInfection, Inflammation and Rheumatology Section, UCL Great Ormond Street Institute of Child Health, London, United KingdomGreat Ormond Street Hospital NHS Foundation Trust, London, United KingdomInfection, Inflammation and Rheumatology Section, UCL Great Ormond Street Institute of Child Health, London, United KingdomGreat Ormond Street Hospital NHS Foundation Trust, London, United KingdomCentre for Adolescent Rheumatology, Arthritis Research UK, University College London (UCL), University College London Hospital (UCLH) and Great Ormond Street Hospital (GOSH), London, United KingdomIt is now increasingly recognized that some monogenic autoinflammatory diseases and immunodeficiencies cause vasculitis, although genetic causes of vasculitis are extremely rare. We describe a child of non-consanguineous parents who presented with cutaneous vasculitis, digital ischaemia and hypocomplementaemia. A heterozygous p.R1042G gain-of-function mutation (GOF) in the complement component C3 gene was identified as the cause, resulting in secondary C3 consumption and complete absence of alternative complement pathway activity, decreased classical complement activity, and low levels of serum C3 with normal C4 levels. The same heterozygous mutation and immunological defects were also identified in another symptomatic sibling and his father. C3 deficiency due GOF C3 mutations is thus now added to the growing list of monogenic causes of vasculitis and should always be considered in vasculitis patients found to have persistently low levels of C3 with normal C4.https://www.frontiersin.org/article/10.3389/fimmu.2018.02524/fullcutaneous vasculitisdigital ischaemiaautoinflammationgain-of-function (GOF)next-generating sequencingtargeted gene capture |
| spellingShingle | Ebun Omoyinmi Ebun Omoyinmi Iman Mohamoud Kimberly Gilmour Paul A. Brogan Paul A. Brogan Despina Eleftheriou Despina Eleftheriou Despina Eleftheriou Cutaneous Vasculitis and Digital Ischaemia Caused by Heterozygous Gain-of-Function Mutation in C3 Frontiers in Immunology cutaneous vasculitis digital ischaemia autoinflammation gain-of-function (GOF) next-generating sequencing targeted gene capture |
| title | Cutaneous Vasculitis and Digital Ischaemia Caused by Heterozygous Gain-of-Function Mutation in C3 |
| title_full | Cutaneous Vasculitis and Digital Ischaemia Caused by Heterozygous Gain-of-Function Mutation in C3 |
| title_fullStr | Cutaneous Vasculitis and Digital Ischaemia Caused by Heterozygous Gain-of-Function Mutation in C3 |
| title_full_unstemmed | Cutaneous Vasculitis and Digital Ischaemia Caused by Heterozygous Gain-of-Function Mutation in C3 |
| title_short | Cutaneous Vasculitis and Digital Ischaemia Caused by Heterozygous Gain-of-Function Mutation in C3 |
| title_sort | cutaneous vasculitis and digital ischaemia caused by heterozygous gain of function mutation in c3 |
| topic | cutaneous vasculitis digital ischaemia autoinflammation gain-of-function (GOF) next-generating sequencing targeted gene capture |
| url | https://www.frontiersin.org/article/10.3389/fimmu.2018.02524/full |
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