Targeted next-generation sequencing revealed a novel homozygous mutation in the LRBA gene causes severe haemolysis associated with Inborn Errors of Immunity in an Indian family.
Objectives LPS-responsive beige-like anchor protein (LRBA) deficiency abolishes LRBA protein expression due to biallelic mutations in the LRBA gene that lead to autoimmune manifestations, inflammatory bowel disease, hypogammaglobulinemia in early stages, and variable clinical manifestations.Material...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Taylor & Francis Group
2022-12-01
|
| Series: | Hematology |
| Subjects: | |
| Online Access: | https://www.tandfonline.com/doi/10.1080/16078454.2022.2058736 |
| _version_ | 1828463800281464832 |
|---|---|
| author | Prabhakar Kedar Rashmi Dongerdiye Shanmukhaiah Chandrakala Umair Ahmed Bargir Manisha Madkaikar |
| author_facet | Prabhakar Kedar Rashmi Dongerdiye Shanmukhaiah Chandrakala Umair Ahmed Bargir Manisha Madkaikar |
| author_sort | Prabhakar Kedar |
| collection | DOAJ |
| description | Objectives LPS-responsive beige-like anchor protein (LRBA) deficiency abolishes LRBA protein expression due to biallelic mutations in the LRBA gene that lead to autoimmune manifestations, inflammatory bowel disease, hypogammaglobulinemia in early stages, and variable clinical manifestations.Materials and methods Mutational analysis of the LRBA gene was performed in Indian patients using targeted Next Generation Sequencing (t-NGS) and confirmed by Sanger sequencing using specific primers of exons 53. Then, bioinformatics analysis and protein modeling for the novel founded mutations were also performed. The genotype, phenotype correlation was done according to the molecular findings and clinical features.Results We report an unusual case of a female patient born of a consanguineous marriage, presented with severe anaemia and jaundice with a history of multiple blood transfusions of unknown cause up to the age of 5 yrs. She had hepatosplenomegaly with recurrent viral and bacterial infections. Tests for hemoglobinopathies, enzymopathies, and hereditary spherocytosis were within the normal limits. The t-NGS revealed a novel homozygous missense variation in exon 53 of the LRBA gene (chr4:151231464C > T; c.7799G > A) (p.C2600Y), and the parents were heterozygous. The further immunological analysis is suggestive of hypogammaglobulinaemia and autoimmune haemolytic anaemia. The bioinformatics tools are suggestive of deleterious and disease-causing variants.Conclusion This study concludes the importance of a timely decision of targeted exome sequencing for the molecular diagnostic tool of unexplained haemolytic anaemia with heterogeneous clinical phenotypes. |
| first_indexed | 2024-12-11T02:58:59Z |
| format | Article |
| id | doaj.art-fc547031bc0d41218d04963118dc4dce |
| institution | Directory Open Access Journal |
| issn | 1607-8454 |
| language | English |
| last_indexed | 2024-12-11T02:58:59Z |
| publishDate | 2022-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Hematology |
| spelling | doaj.art-fc547031bc0d41218d04963118dc4dce2022-12-22T01:23:05ZengTaylor & Francis GroupHematology1607-84542022-12-0127144144810.1080/16078454.2022.2058736Targeted next-generation sequencing revealed a novel homozygous mutation in the LRBA gene causes severe haemolysis associated with Inborn Errors of Immunity in an Indian family.Prabhakar Kedar0Rashmi Dongerdiye1Shanmukhaiah Chandrakala2Umair Ahmed Bargir3Manisha Madkaikar4Department of Haematogenetics, ICMR- National Institute of Immunohaematology, Parel, Mumbai, IndiaDepartment of Haematogenetics, ICMR- National Institute of Immunohaematology, Parel, Mumbai, IndiaDepartment of Hematology, King Edward Memorial Hospital, Parel, Mumbai, IndiaDepartment of Pediatric Immunology and Leukocyte Biology, ICMR- National Institute of Immunohaematology, Parel, Mumbai, IndiaDepartment of Pediatric Immunology and Leukocyte Biology, ICMR- National Institute of Immunohaematology, Parel, Mumbai, IndiaObjectives LPS-responsive beige-like anchor protein (LRBA) deficiency abolishes LRBA protein expression due to biallelic mutations in the LRBA gene that lead to autoimmune manifestations, inflammatory bowel disease, hypogammaglobulinemia in early stages, and variable clinical manifestations.Materials and methods Mutational analysis of the LRBA gene was performed in Indian patients using targeted Next Generation Sequencing (t-NGS) and confirmed by Sanger sequencing using specific primers of exons 53. Then, bioinformatics analysis and protein modeling for the novel founded mutations were also performed. The genotype, phenotype correlation was done according to the molecular findings and clinical features.Results We report an unusual case of a female patient born of a consanguineous marriage, presented with severe anaemia and jaundice with a history of multiple blood transfusions of unknown cause up to the age of 5 yrs. She had hepatosplenomegaly with recurrent viral and bacterial infections. Tests for hemoglobinopathies, enzymopathies, and hereditary spherocytosis were within the normal limits. The t-NGS revealed a novel homozygous missense variation in exon 53 of the LRBA gene (chr4:151231464C > T; c.7799G > A) (p.C2600Y), and the parents were heterozygous. The further immunological analysis is suggestive of hypogammaglobulinaemia and autoimmune haemolytic anaemia. The bioinformatics tools are suggestive of deleterious and disease-causing variants.Conclusion This study concludes the importance of a timely decision of targeted exome sequencing for the molecular diagnostic tool of unexplained haemolytic anaemia with heterogeneous clinical phenotypes.https://www.tandfonline.com/doi/10.1080/16078454.2022.2058736Autoimmune hemolytic anemiahypogammaglobulinaemiaLRBA deficiencynext generation sequencing |
| spellingShingle | Prabhakar Kedar Rashmi Dongerdiye Shanmukhaiah Chandrakala Umair Ahmed Bargir Manisha Madkaikar Targeted next-generation sequencing revealed a novel homozygous mutation in the LRBA gene causes severe haemolysis associated with Inborn Errors of Immunity in an Indian family. Hematology Autoimmune hemolytic anemia hypogammaglobulinaemia LRBA deficiency next generation sequencing |
| title | Targeted next-generation sequencing revealed a novel homozygous mutation in the LRBA gene causes severe haemolysis associated with Inborn Errors of Immunity in an Indian family. |
| title_full | Targeted next-generation sequencing revealed a novel homozygous mutation in the LRBA gene causes severe haemolysis associated with Inborn Errors of Immunity in an Indian family. |
| title_fullStr | Targeted next-generation sequencing revealed a novel homozygous mutation in the LRBA gene causes severe haemolysis associated with Inborn Errors of Immunity in an Indian family. |
| title_full_unstemmed | Targeted next-generation sequencing revealed a novel homozygous mutation in the LRBA gene causes severe haemolysis associated with Inborn Errors of Immunity in an Indian family. |
| title_short | Targeted next-generation sequencing revealed a novel homozygous mutation in the LRBA gene causes severe haemolysis associated with Inborn Errors of Immunity in an Indian family. |
| title_sort | targeted next generation sequencing revealed a novel homozygous mutation in the lrba gene causes severe haemolysis associated with inborn errors of immunity in an indian family |
| topic | Autoimmune hemolytic anemia hypogammaglobulinaemia LRBA deficiency next generation sequencing |
| url | https://www.tandfonline.com/doi/10.1080/16078454.2022.2058736 |
| work_keys_str_mv | AT prabhakarkedar targetednextgenerationsequencingrevealedanovelhomozygousmutationinthelrbagenecausesseverehaemolysisassociatedwithinbornerrorsofimmunityinanindianfamily AT rashmidongerdiye targetednextgenerationsequencingrevealedanovelhomozygousmutationinthelrbagenecausesseverehaemolysisassociatedwithinbornerrorsofimmunityinanindianfamily AT shanmukhaiahchandrakala targetednextgenerationsequencingrevealedanovelhomozygousmutationinthelrbagenecausesseverehaemolysisassociatedwithinbornerrorsofimmunityinanindianfamily AT umairahmedbargir targetednextgenerationsequencingrevealedanovelhomozygousmutationinthelrbagenecausesseverehaemolysisassociatedwithinbornerrorsofimmunityinanindianfamily AT manishamadkaikar targetednextgenerationsequencingrevealedanovelhomozygousmutationinthelrbagenecausesseverehaemolysisassociatedwithinbornerrorsofimmunityinanindianfamily |