Case report: A novel de novo germline loss-of-function mutation in the STAT1 transactivation domain in two Chinese siblings, with the elder sibling presenting with multifocal Bacillus Calmette–Guerin osteomyelitis
Signal transducer and activator of transcription 1 (STAT1) gene mutations have broad clinical phenotypes, classified by the inheritance pattern and functional state. Individuals with autosomal dominant STAT1 deficiency are more susceptible to intracellular bacteria, the hallmark of which is Mendelia...
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Frontiers Media S.A.
2025-01-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1504816/full |
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| author | Qin Ying Lim Qin Ying Lim Daniel Leung Crystal K. Lam Xingtian Yang Kai N. Cheong Kai N. Cheong Andrew K. H. Yik Jing Yang Koon-Wing Chan Pamela P. W. Lee Pamela P. W. Lee Pamela P. W. Lee Pamela P. W. Lee Miyuki Tsumura Elaine Y. L. Au Jaime S. Rosa Duque Jaime S. Rosa Duque Jaime S. Rosa Duque Satoshi Okada Yu Lung Lau Yu Lung Lau Yu Lung Lau |
| author_facet | Qin Ying Lim Qin Ying Lim Daniel Leung Crystal K. Lam Xingtian Yang Kai N. Cheong Kai N. Cheong Andrew K. H. Yik Jing Yang Koon-Wing Chan Pamela P. W. Lee Pamela P. W. Lee Pamela P. W. Lee Pamela P. W. Lee Miyuki Tsumura Elaine Y. L. Au Jaime S. Rosa Duque Jaime S. Rosa Duque Jaime S. Rosa Duque Satoshi Okada Yu Lung Lau Yu Lung Lau Yu Lung Lau |
| author_sort | Qin Ying Lim |
| collection | DOAJ |
| description | Signal transducer and activator of transcription 1 (STAT1) gene mutations have broad clinical phenotypes, classified by the inheritance pattern and functional state. Individuals with autosomal dominant STAT1 deficiency are more susceptible to intracellular bacteria, the hallmark of which is Mendelian susceptibility to mycobacterial diseases (MSMDs) that are associated with increased risks of invasive disease by weakly virulent mycobacteria. We report a novel de novo heterozygous missense mutation in exon 23 of the STAT1 gene (NM_007315.4):c.2129C>T(p.Ser710Phe) (S710F), located in the transactivation domain (TAD) for two Chinese siblings, whereby the index patient presented with multifocal osteomyelitis after Bacillus Calmette–Guerin (BCG) vaccine, while the younger sibling was spared the infection, as BCG vaccination was withheld at birth. STAT1 loss-of-function was confirmed by the gamma-activated sequence reporter assay, representing the first loss-of-function mutation in the TAD of the STAT1 gene. Both parents did not have the same mutation, and this finding is suggestive of gonadal mosaicism. |
| format | Article |
| id | doaj-art-f34b26b35a884cf3991d35e5e46dfd69 |
| institution | Kabale University |
| issn | 1664-3224 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj-art-f34b26b35a884cf3991d35e5e46dfd692025-01-07T06:49:08ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-01-011510.3389/fimmu.2024.15048161504816Case report: A novel de novo germline loss-of-function mutation in the STAT1 transactivation domain in two Chinese siblings, with the elder sibling presenting with multifocal Bacillus Calmette–Guerin osteomyelitisQin Ying Lim0Qin Ying Lim1Daniel Leung2Crystal K. Lam3Xingtian Yang4Kai N. Cheong5Kai N. Cheong6Andrew K. H. Yik7Jing Yang8Koon-Wing Chan9Pamela P. W. Lee10Pamela P. W. Lee11Pamela P. W. Lee12Pamela P. W. Lee13Miyuki Tsumura14Elaine Y. L. Au15Jaime S. Rosa Duque16Jaime S. Rosa Duque17Jaime S. Rosa Duque18Satoshi Okada19Yu Lung Lau20Yu Lung Lau21Yu Lung Lau22Department of Paediatrics and Adolescent Medicine, Queen Mary Hospital, Hong Kong, Hong Kong SAR, ChinaDepartment of Paediatrics and Adolescent Medicine, The University of Hong Kong, Hong Kong, Hong Kong SAR, ChinaDepartment of Paediatrics and Adolescent Medicine, The University of Hong Kong, Hong Kong, Hong Kong SAR, ChinaDivision of Clinical Immunology, Department of Pathology, Queen Mary Hospital, Hong Kong, Hong Kong SAR, ChinaDepartment of Paediatrics and Adolescent Medicine, The University of Hong Kong, Hong Kong, Hong Kong SAR, ChinaDepartment of Paediatrics and Adolescent Medicine, The University of Hong Kong, Hong Kong, Hong Kong SAR, ChinaDepartment of Paediatrics and Adolescent Medicine, Hong Kong Children’s Hospital, Hong Kong, Hong Kong SAR, ChinaDepartment of Paediatrics and Adolescent Medicine, The University of Hong Kong, Hong Kong, Hong Kong SAR, ChinaDepartment of Paediatrics and Adolescent Medicine, The University of Hong Kong, Hong Kong, Hong Kong SAR, ChinaDepartment of Paediatrics and Adolescent Medicine, The University of Hong Kong, Hong Kong, Hong Kong SAR, ChinaDepartment of Paediatrics and Adolescent Medicine, Queen Mary Hospital, Hong Kong, Hong Kong SAR, ChinaDepartment of Paediatrics and Adolescent Medicine, The University of Hong Kong, Hong Kong, Hong Kong SAR, ChinaDepartment of Paediatrics and Adolescent Medicine, Hong Kong Children’s Hospital, Hong Kong, Hong Kong SAR, ChinaDepartment of Paediatrics, The University of Hong Kong – Shenzhen Hospital, Shenzhen, ChinaDepartment of Paediatrics, Hiroshima University Graduate School of Biomedical and Health Sciences, Hiroshima, JapanDivision of Clinical Immunology, Department of Pathology, Queen Mary Hospital, Hong Kong, Hong Kong SAR, ChinaDepartment of Paediatrics and Adolescent Medicine, Queen Mary Hospital, Hong Kong, Hong Kong SAR, ChinaDepartment of Paediatrics and Adolescent Medicine, The University of Hong Kong, Hong Kong, Hong Kong SAR, ChinaDepartment of Paediatrics and Adolescent Medicine, Hong Kong Children’s Hospital, Hong Kong, Hong Kong SAR, ChinaDepartment of Paediatrics, Hiroshima University Graduate School of Biomedical and Health Sciences, Hiroshima, JapanDepartment of Paediatrics and Adolescent Medicine, Queen Mary Hospital, Hong Kong, Hong Kong SAR, ChinaDepartment of Paediatrics and Adolescent Medicine, The University of Hong Kong, Hong Kong, Hong Kong SAR, ChinaDepartment of Paediatrics and Adolescent Medicine, Hong Kong Children’s Hospital, Hong Kong, Hong Kong SAR, ChinaSignal transducer and activator of transcription 1 (STAT1) gene mutations have broad clinical phenotypes, classified by the inheritance pattern and functional state. Individuals with autosomal dominant STAT1 deficiency are more susceptible to intracellular bacteria, the hallmark of which is Mendelian susceptibility to mycobacterial diseases (MSMDs) that are associated with increased risks of invasive disease by weakly virulent mycobacteria. We report a novel de novo heterozygous missense mutation in exon 23 of the STAT1 gene (NM_007315.4):c.2129C>T(p.Ser710Phe) (S710F), located in the transactivation domain (TAD) for two Chinese siblings, whereby the index patient presented with multifocal osteomyelitis after Bacillus Calmette–Guerin (BCG) vaccine, while the younger sibling was spared the infection, as BCG vaccination was withheld at birth. STAT1 loss-of-function was confirmed by the gamma-activated sequence reporter assay, representing the first loss-of-function mutation in the TAD of the STAT1 gene. Both parents did not have the same mutation, and this finding is suggestive of gonadal mosaicism.https://www.frontiersin.org/articles/10.3389/fimmu.2024.1504816/fullSTAT1 loss-of-functionBCG osteomyelitisMendelian susceptibility to mycobacterial diseasesgermline mosaicismcase report |
| spellingShingle | Qin Ying Lim Qin Ying Lim Daniel Leung Crystal K. Lam Xingtian Yang Kai N. Cheong Kai N. Cheong Andrew K. H. Yik Jing Yang Koon-Wing Chan Pamela P. W. Lee Pamela P. W. Lee Pamela P. W. Lee Pamela P. W. Lee Miyuki Tsumura Elaine Y. L. Au Jaime S. Rosa Duque Jaime S. Rosa Duque Jaime S. Rosa Duque Satoshi Okada Yu Lung Lau Yu Lung Lau Yu Lung Lau Case report: A novel de novo germline loss-of-function mutation in the STAT1 transactivation domain in two Chinese siblings, with the elder sibling presenting with multifocal Bacillus Calmette–Guerin osteomyelitis Frontiers in Immunology STAT1 loss-of-function BCG osteomyelitis Mendelian susceptibility to mycobacterial diseases germline mosaicism case report |
| title | Case report: A novel de novo germline loss-of-function mutation in the STAT1 transactivation domain in two Chinese siblings, with the elder sibling presenting with multifocal Bacillus Calmette–Guerin osteomyelitis |
| title_full | Case report: A novel de novo germline loss-of-function mutation in the STAT1 transactivation domain in two Chinese siblings, with the elder sibling presenting with multifocal Bacillus Calmette–Guerin osteomyelitis |
| title_fullStr | Case report: A novel de novo germline loss-of-function mutation in the STAT1 transactivation domain in two Chinese siblings, with the elder sibling presenting with multifocal Bacillus Calmette–Guerin osteomyelitis |
| title_full_unstemmed | Case report: A novel de novo germline loss-of-function mutation in the STAT1 transactivation domain in two Chinese siblings, with the elder sibling presenting with multifocal Bacillus Calmette–Guerin osteomyelitis |
| title_short | Case report: A novel de novo germline loss-of-function mutation in the STAT1 transactivation domain in two Chinese siblings, with the elder sibling presenting with multifocal Bacillus Calmette–Guerin osteomyelitis |
| title_sort | case report a novel de novo germline loss of function mutation in the stat1 transactivation domain in two chinese siblings with the elder sibling presenting with multifocal bacillus calmette guerin osteomyelitis |
| topic | STAT1 loss-of-function BCG osteomyelitis Mendelian susceptibility to mycobacterial diseases germline mosaicism case report |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1504816/full |
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