Variants Disrupting CD40L Transmembrane Domain and Atypical X-Linked Hyper-IgM Syndrome: A Case Report With Leishmaniasis and Review of the Literature
X-linked hyper-IgM (XHIGM) syndrome is caused by mutations of the CD40LG gene, encoding the CD40L protein. The clinical presentation is characterized by early-onset infections, with profound hypogammaglobulinemia and often elevated IgM, susceptibility to opportunistic infections, such as Pneumocysti...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-04-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2022.840767/full |
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| author | Boaz Palterer Boaz Palterer Lorenzo Salvati Manuela Capone Valentina Mecheri Laura Maggi Alessio Mazzoni Lorenzo Cosmi Lorenzo Cosmi Nila Volpi Lucia Tiberi Lucia Tiberi Aldesia Provenzano Sabrina Giglio Paola Parronchi Paola Parronchi Giandomenico Maggiore Oreste Gallo Alessandro Bartoloni Francesco Annunziato Francesco Annunziato Lorenzo Zammarchi Lorenzo Zammarchi Francesco Liotta Francesco Liotta |
| author_facet | Boaz Palterer Boaz Palterer Lorenzo Salvati Manuela Capone Valentina Mecheri Laura Maggi Alessio Mazzoni Lorenzo Cosmi Lorenzo Cosmi Nila Volpi Lucia Tiberi Lucia Tiberi Aldesia Provenzano Sabrina Giglio Paola Parronchi Paola Parronchi Giandomenico Maggiore Oreste Gallo Alessandro Bartoloni Francesco Annunziato Francesco Annunziato Lorenzo Zammarchi Lorenzo Zammarchi Francesco Liotta Francesco Liotta |
| author_sort | Boaz Palterer |
| collection | DOAJ |
| description | X-linked hyper-IgM (XHIGM) syndrome is caused by mutations of the CD40LG gene, encoding the CD40L protein. The clinical presentation is characterized by early-onset infections, with profound hypogammaglobulinemia and often elevated IgM, susceptibility to opportunistic infections, such as Pneumocystis jirovecii pneumonia, biliary tract disease due to Cryptosporidium parvum, and malignancy. We report a 41-year-old male presenting with recurrent leishmaniasis, hypogammaglobulinemia, and myopathy. Whole-exome sequencing (WES) identified a missense variant in the CD40LG gene (c.107T>A, p.M36K), involving the transmembrane domain of the protein and a missense variant in the carnitine palmitoyl-transferase II (CPT2; c.593C>G; p.S198C) gene, leading to the diagnosis of hypomorphic XHIGM and CPT2 deficiency stress-induced myopathy. A review of all the previously reported cases of XHIGM with variants in the transmembrane domain showcased that these patients could present with atypical clinical features. Variants in the transmembrane domain of CD40LG act as hypomorphic generating a protein with a lower surface expression. Unlike large deletions or extracellular domain variants, they do not abolish the interaction with CD40, therefore preserving some biological activity. |
| first_indexed | 2024-12-12T19:20:10Z |
| format | Article |
| id | doaj.art-2e57030a27d244f1893271041a33dc56 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-12T19:20:10Z |
| publishDate | 2022-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-2e57030a27d244f1893271041a33dc562022-12-22T00:14:36ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-04-011310.3389/fimmu.2022.840767840767Variants Disrupting CD40L Transmembrane Domain and Atypical X-Linked Hyper-IgM Syndrome: A Case Report With Leishmaniasis and Review of the LiteratureBoaz Palterer0Boaz Palterer1Lorenzo Salvati2Manuela Capone3Valentina Mecheri4Laura Maggi5Alessio Mazzoni6Lorenzo Cosmi7Lorenzo Cosmi8Nila Volpi9Lucia Tiberi10Lucia Tiberi11Aldesia Provenzano12Sabrina Giglio13Paola Parronchi14Paola Parronchi15Giandomenico Maggiore16Oreste Gallo17Alessandro Bartoloni18Francesco Annunziato19Francesco Annunziato20Lorenzo Zammarchi21Lorenzo Zammarchi22Francesco Liotta23Francesco Liotta24Department of Experimental and Clinical Medicine, University of Florence, Florence, ItalyFlow Cytometric Diagnostic Centre and Immunotherapy, Careggi University Hospital, Florence, ItalyDepartment of Experimental and Clinical Medicine, University of Florence, Florence, ItalyDepartment of Experimental and Clinical Medicine, University of Florence, Florence, ItalyDepartment of Experimental and Clinical Medicine, University of Florence, Florence, ItalyDepartment of Experimental and Clinical Medicine, University of Florence, Florence, ItalyDepartment of Experimental and Clinical Medicine, University of Florence, Florence, ItalyDepartment of Experimental and Clinical Medicine, University of Florence, Florence, ItalyImmunology and Cell Therapies Unit, Careggi University Hospital, Florence, ItalyUnit of Neurology and Neurophysiology, Department of Medical, Surgical and Neurological Sciences, University of Siena, Siena, ItalyDepartment of Biomedical Experimental and Clinical Sciences “Mario Serio”, University of Florence, Florence, ItalyMedical Genetics Unit, Meyer University Hospital, Firenze, ItalyDepartment of Biomedical Experimental and Clinical Sciences “Mario Serio”, University of Florence, Florence, ItalyMedical Genetics Unit, Department of Medical Sciences and Public Health, University of Cagliari, Cagliari, ItalyDepartment of Experimental and Clinical Medicine, University of Florence, Florence, ItalyImmunology and Cell Therapies Unit, Careggi University Hospital, Florence, ItalyDepartment of Otorhinolaryngology, Careggi University Hospital, Florence, ItalyDepartment of Otorhinolaryngology, Careggi University Hospital, Florence, ItalyInfectious and Tropical Diseases Unit, Careggi University Hospital, Florence, ItalyDepartment of Experimental and Clinical Medicine, University of Florence, Florence, ItalyFlow Cytometric Diagnostic Centre and Immunotherapy, Careggi University Hospital, Florence, ItalyDepartment of Experimental and Clinical Medicine, University of Florence, Florence, ItalyInfectious and Tropical Diseases Unit, Careggi University Hospital, Florence, ItalyDepartment of Experimental and Clinical Medicine, University of Florence, Florence, ItalyImmunology and Cell Therapies Unit, Careggi University Hospital, Florence, ItalyX-linked hyper-IgM (XHIGM) syndrome is caused by mutations of the CD40LG gene, encoding the CD40L protein. The clinical presentation is characterized by early-onset infections, with profound hypogammaglobulinemia and often elevated IgM, susceptibility to opportunistic infections, such as Pneumocystis jirovecii pneumonia, biliary tract disease due to Cryptosporidium parvum, and malignancy. We report a 41-year-old male presenting with recurrent leishmaniasis, hypogammaglobulinemia, and myopathy. Whole-exome sequencing (WES) identified a missense variant in the CD40LG gene (c.107T>A, p.M36K), involving the transmembrane domain of the protein and a missense variant in the carnitine palmitoyl-transferase II (CPT2; c.593C>G; p.S198C) gene, leading to the diagnosis of hypomorphic XHIGM and CPT2 deficiency stress-induced myopathy. A review of all the previously reported cases of XHIGM with variants in the transmembrane domain showcased that these patients could present with atypical clinical features. Variants in the transmembrane domain of CD40LG act as hypomorphic generating a protein with a lower surface expression. Unlike large deletions or extracellular domain variants, they do not abolish the interaction with CD40, therefore preserving some biological activity.https://www.frontiersin.org/articles/10.3389/fimmu.2022.840767/fullCD40LG geneCD40LG mutationLeishmanialeishmaniasisCPT2 deficiencyCPT2 gene |
| spellingShingle | Boaz Palterer Boaz Palterer Lorenzo Salvati Manuela Capone Valentina Mecheri Laura Maggi Alessio Mazzoni Lorenzo Cosmi Lorenzo Cosmi Nila Volpi Lucia Tiberi Lucia Tiberi Aldesia Provenzano Sabrina Giglio Paola Parronchi Paola Parronchi Giandomenico Maggiore Oreste Gallo Alessandro Bartoloni Francesco Annunziato Francesco Annunziato Lorenzo Zammarchi Lorenzo Zammarchi Francesco Liotta Francesco Liotta Variants Disrupting CD40L Transmembrane Domain and Atypical X-Linked Hyper-IgM Syndrome: A Case Report With Leishmaniasis and Review of the Literature Frontiers in Immunology CD40LG gene CD40LG mutation Leishmania leishmaniasis CPT2 deficiency CPT2 gene |
| title | Variants Disrupting CD40L Transmembrane Domain and Atypical X-Linked Hyper-IgM Syndrome: A Case Report With Leishmaniasis and Review of the Literature |
| title_full | Variants Disrupting CD40L Transmembrane Domain and Atypical X-Linked Hyper-IgM Syndrome: A Case Report With Leishmaniasis and Review of the Literature |
| title_fullStr | Variants Disrupting CD40L Transmembrane Domain and Atypical X-Linked Hyper-IgM Syndrome: A Case Report With Leishmaniasis and Review of the Literature |
| title_full_unstemmed | Variants Disrupting CD40L Transmembrane Domain and Atypical X-Linked Hyper-IgM Syndrome: A Case Report With Leishmaniasis and Review of the Literature |
| title_short | Variants Disrupting CD40L Transmembrane Domain and Atypical X-Linked Hyper-IgM Syndrome: A Case Report With Leishmaniasis and Review of the Literature |
| title_sort | variants disrupting cd40l transmembrane domain and atypical x linked hyper igm syndrome a case report with leishmaniasis and review of the literature |
| topic | CD40LG gene CD40LG mutation Leishmania leishmaniasis CPT2 deficiency CPT2 gene |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2022.840767/full |
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