Case report: A case of novel homozygous LRBA variant induced by chromosomal segmental uniparental disomy - genetic and clinical insights
ObjectiveThe study aims to report a rare case of a novel homozygous variant in the LRBA gene, originating from uniparental disomy of paternal origin. This case contributes new clinical data to the LRBA gene variant database.MethodsThe study details the case of a 2-year-old child diagnosed in May 202...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2024-03-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1351076/full |
| _version_ | 1797277359379841024 |
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| author | Lihua Jiang Sen Chen |
| author_facet | Lihua Jiang Sen Chen |
| author_sort | Lihua Jiang |
| collection | DOAJ |
| description | ObjectiveThe study aims to report a rare case of a novel homozygous variant in the LRBA gene, originating from uniparental disomy of paternal origin. This case contributes new clinical data to the LRBA gene variant database.MethodsThe study details the case of a 2-year-old child diagnosed in May 2023 at our center with a homozygous LRBA gene variant. Detailed clinical data of the patient were collected, including whole-exome sequencing of peripheral blood mononuclear cells, with parental genetic verification.ResultsThe child presented with recurrent respiratory infections and chronic neutropenia, progressing to pancytopenia. Imaging showed splenomegaly and enlarged lymph nodes in the axillary and abdominal regions. Peripheral blood lymphocyte count revealed reduced B cells and NK cells. Elevated cytokine levels of IFN-α and IFN-r were observed. Whole-exome sequencing revealed a nonsense homozygous variant in the LRBA gene, specifically c.2584C>T (p.Gln862Ter). The father exhibited a heterozygous variant at this locus, while no variant was found in the mother. Sample analysis indicated characteristics of uniparental disomy. According to the guidelines of the American College of Medical Genetics and Genomics (ACMG), this variant is preliminarily classified as “Likely pathogenic”. Currently, there are no reports in academic literature regarding this specific variant site.ConclusionLRBA gene variants can lead to a rare inborn error of immunity disease. The c.2584C>T (p.Gln862Ter) variant in exon 22 of the LRBA gene is a newly identified pathogenic variant, and the homozygous variant caused by uniparental disomy is exceedingly rare. This case represents the second global report of an LRBA gene function loss due to uniparental disomy abnormalities. |
| first_indexed | 2024-03-07T15:47:32Z |
| format | Article |
| id | doaj.art-76ebdb4aab78444381af91b5edf2a7e8 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-03-07T15:47:32Z |
| publishDate | 2024-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-76ebdb4aab78444381af91b5edf2a7e82024-03-05T04:20:50ZengFrontiers Media S.A.Frontiers in Immunology1664-32242024-03-011510.3389/fimmu.2024.13510761351076Case report: A case of novel homozygous LRBA variant induced by chromosomal segmental uniparental disomy - genetic and clinical insightsLihua JiangSen ChenObjectiveThe study aims to report a rare case of a novel homozygous variant in the LRBA gene, originating from uniparental disomy of paternal origin. This case contributes new clinical data to the LRBA gene variant database.MethodsThe study details the case of a 2-year-old child diagnosed in May 2023 at our center with a homozygous LRBA gene variant. Detailed clinical data of the patient were collected, including whole-exome sequencing of peripheral blood mononuclear cells, with parental genetic verification.ResultsThe child presented with recurrent respiratory infections and chronic neutropenia, progressing to pancytopenia. Imaging showed splenomegaly and enlarged lymph nodes in the axillary and abdominal regions. Peripheral blood lymphocyte count revealed reduced B cells and NK cells. Elevated cytokine levels of IFN-α and IFN-r were observed. Whole-exome sequencing revealed a nonsense homozygous variant in the LRBA gene, specifically c.2584C>T (p.Gln862Ter). The father exhibited a heterozygous variant at this locus, while no variant was found in the mother. Sample analysis indicated characteristics of uniparental disomy. According to the guidelines of the American College of Medical Genetics and Genomics (ACMG), this variant is preliminarily classified as “Likely pathogenic”. Currently, there are no reports in academic literature regarding this specific variant site.ConclusionLRBA gene variants can lead to a rare inborn error of immunity disease. The c.2584C>T (p.Gln862Ter) variant in exon 22 of the LRBA gene is a newly identified pathogenic variant, and the homozygous variant caused by uniparental disomy is exceedingly rare. This case represents the second global report of an LRBA gene function loss due to uniparental disomy abnormalities.https://www.frontiersin.org/articles/10.3389/fimmu.2024.1351076/fullLRBA gene variantuniparental disomypaternal originimmune dysregulationpancytopenia |
| spellingShingle | Lihua Jiang Sen Chen Case report: A case of novel homozygous LRBA variant induced by chromosomal segmental uniparental disomy - genetic and clinical insights Frontiers in Immunology LRBA gene variant uniparental disomy paternal origin immune dysregulation pancytopenia |
| title | Case report: A case of novel homozygous LRBA variant induced by chromosomal segmental uniparental disomy - genetic and clinical insights |
| title_full | Case report: A case of novel homozygous LRBA variant induced by chromosomal segmental uniparental disomy - genetic and clinical insights |
| title_fullStr | Case report: A case of novel homozygous LRBA variant induced by chromosomal segmental uniparental disomy - genetic and clinical insights |
| title_full_unstemmed | Case report: A case of novel homozygous LRBA variant induced by chromosomal segmental uniparental disomy - genetic and clinical insights |
| title_short | Case report: A case of novel homozygous LRBA variant induced by chromosomal segmental uniparental disomy - genetic and clinical insights |
| title_sort | case report a case of novel homozygous lrba variant induced by chromosomal segmental uniparental disomy genetic and clinical insights |
| topic | LRBA gene variant uniparental disomy paternal origin immune dysregulation pancytopenia |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1351076/full |
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