HETEROZYGOUS PATHOGENIC MASP2 VARIANT ASSOCIATED WITH INFANTILE GIANT CELL HEPATITIS WITH AUTOIMMUNE HAEMOLYTIC ANAEMIA IN A CHILD
Objective: Infantile giant cell hepatitis with autoimmune hae molytic anaemia (GCH-AHA) is a rare disease characterised by giant cell and autoimmune haemolysis. The pathogenic mecha nisms involve several factors, including genetic and immunolog ical components, particularly those related to the lect...
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Istanbul University Press
2024-10-01
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| Series: | İstanbul Tıp Fakültesi Dergisi |
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| Online Access: | https://cdn.istanbul.edu.tr/file/JTA6CLJ8T5/309BCAB741A54B6DB818F13EDBF050B5 |
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| author | Merve Sarıtaş Sinem Fırtına Süheyla Ocak Ayça Kıykım Zeynep Ocak Begüm Işıkgil Müge Sayitoğlu |
| author_facet | Merve Sarıtaş Sinem Fırtına Süheyla Ocak Ayça Kıykım Zeynep Ocak Begüm Işıkgil Müge Sayitoğlu |
| author_sort | Merve Sarıtaş |
| collection | DOAJ |
| description | Objective: Infantile giant cell hepatitis with autoimmune hae molytic anaemia (GCH-AHA) is a rare disease characterised by giant cell and autoimmune haemolysis. The pathogenic mecha nisms involve several factors, including genetic and immunolog ical components, particularly those related to the lectin pathway of the complement system. In this study, we aimed to identify possible germline variations in patients with GCH-AHA. Material and Method: Whole-exome sequencing (WES) was performed on a 6-month-old boy who was diagnosed with GCH AHA. An in-house data analysis pipeline was applied to deter mine familial segregation using Sanger sequencing. ELISA was used for MASP2 protein detection. Result: WES revealed a likely pathogenic heterozygous missense variant (p.(Cys618Tyr)) in the Mannose-binding lectin (MBL)-associated serine protease-2 (MASP-2) gene. The MASP2 variant identified in the serine protease domain was predicted to disrupt disulphide bonds. In vitro assays showed decreased MASP2 levels in the patient and mother compared with controls, supporting the potential pathogenicity of the variant.Conclusion: This study highlighted the association between a novel MASP2 variant and GCH-AHA, emphasising the role of the lectin pathway in the pathogenesis of this rare disorder. The variable expressivity and incomplete penetrance observed in MASP2 deficiency underscore the complexity of genotype-phe notype correlations. Further investigations into the lectin path way's detailed activation and its impact on GCH-AHA pathogen esis are warranted for a comprehensive understanding of the disease mechanisms. |
| format | Article |
| id | doaj-art-a407e498a6b640f693a4b2120925aa9e |
| institution | OA Journals |
| issn | 1305-6441 |
| language | English |
| publishDate | 2024-10-01 |
| publisher | Istanbul University Press |
| record_format | Article |
| series | İstanbul Tıp Fakültesi Dergisi |
| spelling | doaj-art-a407e498a6b640f693a4b2120925aa9e2025-08-20T02:15:18ZengIstanbul University Pressİstanbul Tıp Fakültesi Dergisi1305-64412024-10-0187429129810.26650/IUITFD.1489141123456HETEROZYGOUS PATHOGENIC MASP2 VARIANT ASSOCIATED WITH INFANTILE GIANT CELL HEPATITIS WITH AUTOIMMUNE HAEMOLYTIC ANAEMIA IN A CHILDMerve Sarıtaş0https://orcid.org/0000-0003-4753-9372Sinem Fırtına1https://orcid.org/0000-0002-3370-8545Süheyla Ocak2https://orcid.org/0000-0001-7479-7444Ayça Kıykım3https://orcid.org/0000-0001-5821-3963Zeynep Ocak4https://orcid.org/0000-0001-9784-2228Begüm Işıkgil5https://orcid.org/0000-0002-7541-4596Müge Sayitoğlu6https://orcid.org/0000-0002-8648-213Xİstanbul Üniversitesi, İstanbul, Türkiyeİstanbul Üniversitesi-Cerrahpaşa, Istanbul, Turkiyeİstanbul Üniversitesi-Cerrahpaşa, Istanbul, Turkiyeİstanbul Üniversitesi-Cerrahpaşa, Istanbul, Turkiyeİstinye Üniversitesi, Istanbul, Turkiyeİstinye Üniversitesi, Istanbul, Turkiyeİstanbul Üniversitesi, İstanbul, TürkiyeObjective: Infantile giant cell hepatitis with autoimmune hae molytic anaemia (GCH-AHA) is a rare disease characterised by giant cell and autoimmune haemolysis. The pathogenic mecha nisms involve several factors, including genetic and immunolog ical components, particularly those related to the lectin pathway of the complement system. In this study, we aimed to identify possible germline variations in patients with GCH-AHA. Material and Method: Whole-exome sequencing (WES) was performed on a 6-month-old boy who was diagnosed with GCH AHA. An in-house data analysis pipeline was applied to deter mine familial segregation using Sanger sequencing. ELISA was used for MASP2 protein detection. Result: WES revealed a likely pathogenic heterozygous missense variant (p.(Cys618Tyr)) in the Mannose-binding lectin (MBL)-associated serine protease-2 (MASP-2) gene. The MASP2 variant identified in the serine protease domain was predicted to disrupt disulphide bonds. In vitro assays showed decreased MASP2 levels in the patient and mother compared with controls, supporting the potential pathogenicity of the variant.Conclusion: This study highlighted the association between a novel MASP2 variant and GCH-AHA, emphasising the role of the lectin pathway in the pathogenesis of this rare disorder. The variable expressivity and incomplete penetrance observed in MASP2 deficiency underscore the complexity of genotype-phe notype correlations. Further investigations into the lectin path way's detailed activation and its impact on GCH-AHA pathogen esis are warranted for a comprehensive understanding of the disease mechanisms.https://cdn.istanbul.edu.tr/file/JTA6CLJ8T5/309BCAB741A54B6DB818F13EDBF050B5infantile giant cell hepatitisautoimmune haemolytic anaemiacomplement systemmasp2whole-exome sequencing |
| spellingShingle | Merve Sarıtaş Sinem Fırtına Süheyla Ocak Ayça Kıykım Zeynep Ocak Begüm Işıkgil Müge Sayitoğlu HETEROZYGOUS PATHOGENIC MASP2 VARIANT ASSOCIATED WITH INFANTILE GIANT CELL HEPATITIS WITH AUTOIMMUNE HAEMOLYTIC ANAEMIA IN A CHILD İstanbul Tıp Fakültesi Dergisi infantile giant cell hepatitis autoimmune haemolytic anaemia complement system masp2 whole-exome sequencing |
| title | HETEROZYGOUS PATHOGENIC MASP2 VARIANT ASSOCIATED WITH INFANTILE GIANT CELL HEPATITIS WITH AUTOIMMUNE HAEMOLYTIC ANAEMIA IN A CHILD |
| title_full | HETEROZYGOUS PATHOGENIC MASP2 VARIANT ASSOCIATED WITH INFANTILE GIANT CELL HEPATITIS WITH AUTOIMMUNE HAEMOLYTIC ANAEMIA IN A CHILD |
| title_fullStr | HETEROZYGOUS PATHOGENIC MASP2 VARIANT ASSOCIATED WITH INFANTILE GIANT CELL HEPATITIS WITH AUTOIMMUNE HAEMOLYTIC ANAEMIA IN A CHILD |
| title_full_unstemmed | HETEROZYGOUS PATHOGENIC MASP2 VARIANT ASSOCIATED WITH INFANTILE GIANT CELL HEPATITIS WITH AUTOIMMUNE HAEMOLYTIC ANAEMIA IN A CHILD |
| title_short | HETEROZYGOUS PATHOGENIC MASP2 VARIANT ASSOCIATED WITH INFANTILE GIANT CELL HEPATITIS WITH AUTOIMMUNE HAEMOLYTIC ANAEMIA IN A CHILD |
| title_sort | heterozygous pathogenic masp2 variant associated with infantile giant cell hepatitis with autoimmune haemolytic anaemia in a child |
| topic | infantile giant cell hepatitis autoimmune haemolytic anaemia complement system masp2 whole-exome sequencing |
| url | https://cdn.istanbul.edu.tr/file/JTA6CLJ8T5/309BCAB741A54B6DB818F13EDBF050B5 |
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