Novel compound heterozygous stop‐gain mutations of LRBA in a Vietnamese patient with Common Variable Immune Deficiency
Abstract Background Lipopolysaccharide‐responsive and beige‐like anchor (LRBA) deficiency is a rare autosomal recessive common variable immunodeficiency (CVID), affecting 1:25,000–1:50,000 people worldwide. Biallelic mutations in the gene LRBA have been implicated in affected individuals. Methods We...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2020-05-01
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| Series: | Molecular Genetics & Genomic Medicine |
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| Online Access: | https://doi.org/10.1002/mgg3.1216 |
| _version_ | 1797301134424014848 |
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| author | Anh N. L. Phan Thuy T. T. Pham Nghia Huynh Tuan M. Nguyen Cuc T. T. Cao Duong T. Nguyen Duc T. Le Chi‐Bao Bui |
| author_facet | Anh N. L. Phan Thuy T. T. Pham Nghia Huynh Tuan M. Nguyen Cuc T. T. Cao Duong T. Nguyen Duc T. Le Chi‐Bao Bui |
| author_sort | Anh N. L. Phan |
| collection | DOAJ |
| description | Abstract Background Lipopolysaccharide‐responsive and beige‐like anchor (LRBA) deficiency is a rare autosomal recessive common variable immunodeficiency (CVID), affecting 1:25,000–1:50,000 people worldwide. Biallelic mutations in the gene LRBA have been implicated in affected individuals. Methods We report a 16‐year‐old Vietnamese, male patient with recurrent CVID symptoms including chronic diarrhea, interstitial pneumonia, cutaneous granulomatous lesions, hepatosplenomegaly, and finger clubbing. Immunological analyses and whole exome sequencing (WES) were performed to investigate phenotypic and genotypic features. Results Immunological analyses revealed hypogammaglobulinemia and low ratios of CD4+/CD8+ T cells. Two novel compound heterozygous stop‐gain mutation in LRBA were identified: c.1933C > T (p.R645X) and c.949C > T (p.R317X). Sanger sequencing confirmed the segregation of these variants from the intact parents. The abolished LRBA protein expression was shown by immunoblot analysis. Subsequent treatment potentially saves the child from the same immune thrombocytopenia which led to his brother's untimely death; likely caused by the same LRBA mutations. Conclusion This first report of LRBA deficiency in Vietnam expands our knowledge of the diverse phenotypes and genotypes driving CVID. Finally, the utilization of WES shows great promise as an effective diagnostic for CVID in our setting. |
| first_indexed | 2024-03-07T23:17:05Z |
| format | Article |
| id | doaj.art-8bde6b5ce82d483bbbbca531205f69f2 |
| institution | Directory Open Access Journal |
| issn | 2324-9269 |
| language | English |
| last_indexed | 2024-03-07T23:17:05Z |
| publishDate | 2020-05-01 |
| publisher | Wiley |
| record_format | Article |
| series | Molecular Genetics & Genomic Medicine |
| spelling | doaj.art-8bde6b5ce82d483bbbbca531205f69f22024-02-21T10:18:48ZengWileyMolecular Genetics & Genomic Medicine2324-92692020-05-0185n/an/a10.1002/mgg3.1216Novel compound heterozygous stop‐gain mutations of LRBA in a Vietnamese patient with Common Variable Immune DeficiencyAnh N. L. Phan0Thuy T. T. Pham1Nghia Huynh2Tuan M. Nguyen3Cuc T. T. Cao4Duong T. Nguyen5Duc T. Le6Chi‐Bao Bui7Children’s Hospital 1 Ho Chi Minh City VietnamFunctional Genomic Unit DNA Medical Technology Ho Chi Minh City VietnamDepartment of Hematology Ho Chi Minh City University of Medicine and Pharmacy Ho Chi Minh City VietnamChildren’s Hospital 1 Ho Chi Minh City VietnamChildren’s Hospital 1 Ho Chi Minh City VietnamChildren’s Hospital 1 Ho Chi Minh City VietnamFunctional Genomic Unit DNA Medical Technology Ho Chi Minh City VietnamFunctional Genomic Unit DNA Medical Technology Ho Chi Minh City VietnamAbstract Background Lipopolysaccharide‐responsive and beige‐like anchor (LRBA) deficiency is a rare autosomal recessive common variable immunodeficiency (CVID), affecting 1:25,000–1:50,000 people worldwide. Biallelic mutations in the gene LRBA have been implicated in affected individuals. Methods We report a 16‐year‐old Vietnamese, male patient with recurrent CVID symptoms including chronic diarrhea, interstitial pneumonia, cutaneous granulomatous lesions, hepatosplenomegaly, and finger clubbing. Immunological analyses and whole exome sequencing (WES) were performed to investigate phenotypic and genotypic features. Results Immunological analyses revealed hypogammaglobulinemia and low ratios of CD4+/CD8+ T cells. Two novel compound heterozygous stop‐gain mutation in LRBA were identified: c.1933C > T (p.R645X) and c.949C > T (p.R317X). Sanger sequencing confirmed the segregation of these variants from the intact parents. The abolished LRBA protein expression was shown by immunoblot analysis. Subsequent treatment potentially saves the child from the same immune thrombocytopenia which led to his brother's untimely death; likely caused by the same LRBA mutations. Conclusion This first report of LRBA deficiency in Vietnam expands our knowledge of the diverse phenotypes and genotypes driving CVID. Finally, the utilization of WES shows great promise as an effective diagnostic for CVID in our setting.https://doi.org/10.1002/mgg3.1216antibody deficiencychronic diarrheacommon variable immunodeficiencyLRBAstop‐gain mutation |
| spellingShingle | Anh N. L. Phan Thuy T. T. Pham Nghia Huynh Tuan M. Nguyen Cuc T. T. Cao Duong T. Nguyen Duc T. Le Chi‐Bao Bui Novel compound heterozygous stop‐gain mutations of LRBA in a Vietnamese patient with Common Variable Immune Deficiency Molecular Genetics & Genomic Medicine antibody deficiency chronic diarrhea common variable immunodeficiency LRBA stop‐gain mutation |
| title | Novel compound heterozygous stop‐gain mutations of LRBA in a Vietnamese patient with Common Variable Immune Deficiency |
| title_full | Novel compound heterozygous stop‐gain mutations of LRBA in a Vietnamese patient with Common Variable Immune Deficiency |
| title_fullStr | Novel compound heterozygous stop‐gain mutations of LRBA in a Vietnamese patient with Common Variable Immune Deficiency |
| title_full_unstemmed | Novel compound heterozygous stop‐gain mutations of LRBA in a Vietnamese patient with Common Variable Immune Deficiency |
| title_short | Novel compound heterozygous stop‐gain mutations of LRBA in a Vietnamese patient with Common Variable Immune Deficiency |
| title_sort | novel compound heterozygous stop gain mutations of lrba in a vietnamese patient with common variable immune deficiency |
| topic | antibody deficiency chronic diarrhea common variable immunodeficiency LRBA stop‐gain mutation |
| url | https://doi.org/10.1002/mgg3.1216 |
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