The Clinical and Molecular Assessment of Iranian Families with Severe Congenital Neutropenia, Identification of HYOU1 and SHOC2 as Potential Novel Gene Defects
Neutropenia congenita grave (SCN) is a rare disease with a genetically and clinically heterogeneous nature, usually diagnosed in childhood, with an elevated risk of infections such as otitis, skin infections, pneumonia, deep abscesses, and septicemia. Patients with SCN also have an increased risk o...
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| Format: | Article |
| Language: | English |
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Tehran University of Medical Sciences
2022-06-01
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| Series: | Iranian Journal of Allergy, Asthma and Immunology |
| Subjects: | |
| Online Access: | https://ijaai.tums.ac.ir/index.php/ijaai/article/view/3493 |
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| author | Fatemeh Arab Nima Rezaei Forough Taheri Hamideh Kouhpeikar Elham Rayzan Mona Mirbeyk Davood Zare‐Abdollahi Mohsen Ghadami |
| author_facet | Fatemeh Arab Nima Rezaei Forough Taheri Hamideh Kouhpeikar Elham Rayzan Mona Mirbeyk Davood Zare‐Abdollahi Mohsen Ghadami |
| author_sort | Fatemeh Arab |
| collection | DOAJ |
| description |
Neutropenia congenita grave (SCN) is a rare disease with a genetically and clinically heterogeneous nature, usually diagnosed in childhood, with an elevated risk of infections such as otitis, skin infections, pneumonia, deep abscesses, and septicemia. Patients with SCN also have an increased risk of leukemia, and mutations in the ELANE and the HAX1 genes have been observed in those patients.
This study was conducted to genetically screen six Iranian families with SCN who have at least one affected person. In the first step, all exons and intron boundaries of ELANE and HAX1 genes were sequenced in probands. Cases with no pathogenic mutations were tested through whole-exome sequencing (WES).
Analysis showed five different variants in ELANE (c.377 C>T), HAX1 (c.130_131 insA), HYOU1 (c.69 G>C and c.2744 G>A) and SHOC2 (c.4 A>G) genes in four families. We found that two out of six families had mutations in ELANE and HAX1 genes. Moreover, we found two novel mutations at the HYOU1 gene that had not previously been reported, as well as a pathogenic mutation at SHOC2 with multiple phenotypes, that will contribute to determining the genetic basis for SCN.
Our study revealed that WES could help diagnose SCN, improve the classification of neutropenia, and rule out other immunodeficiencies such as autoimmune neutropenia, primary immunodeficiency diseases, and inherited bone marrow failure syndromes.
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| first_indexed | 2024-04-13T03:30:06Z |
| format | Article |
| id | doaj.art-00b6c45dd5e54464a3bdaaa9f9883784 |
| institution | Directory Open Access Journal |
| issn | 1735-1502 1735-5249 |
| language | English |
| last_indexed | 2024-04-13T03:30:06Z |
| publishDate | 2022-06-01 |
| publisher | Tehran University of Medical Sciences |
| record_format | Article |
| series | Iranian Journal of Allergy, Asthma and Immunology |
| spelling | doaj.art-00b6c45dd5e54464a3bdaaa9f98837842022-12-22T03:04:32ZengTehran University of Medical SciencesIranian Journal of Allergy, Asthma and Immunology1735-15021735-52492022-06-0121310.18502/ijaai.v21i3.9808The Clinical and Molecular Assessment of Iranian Families with Severe Congenital Neutropenia, Identification of HYOU1 and SHOC2 as Potential Novel Gene DefectsFatemeh Arab0Nima Rezaei1Forough Taheri2Hamideh Kouhpeikar3Elham Rayzan4Mona Mirbeyk5Davood Zare‐Abdollahi6Mohsen Ghadami7Department of Medical Genetics, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, IranResearch Center for Immunodeficiencies, Children’s Medical Center Hospital, Tehran University of Medical Sciences, Tehran, Iran AND International Hematology/Oncology of Pediatrics’ experts (IHOPE), Universal Scientific Education and Research Network (USERN), Tehran, IranDepartment of Genetics and Molecular Biology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, IranDepartment of Hematology and Blood Bank, Tabas School of Nursing, Birjand University of Medical Sciences, Birjand, IranInternational Hematology/Oncology of Pediatrics’ Experts (IHOPE), Universal Scientific Education and Research Network (USERN), Tehran, IranResearch Center for Immunodeficiencies, Children’s Medical Center Hospital, Tehran University of Medical Sciences, Tehran, IranDepartment of Medical Genetics, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, IranDepartment of Medical Genetics, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran AND Endocrinology and Metabolism Research Institute, Tehran University of Medical Sciences, Tehran, Iran AND Cardiac Primary Prevention Research Center, Tehran Heart Center, Tehran University of Medical Sciences, Tehran, Iran Neutropenia congenita grave (SCN) is a rare disease with a genetically and clinically heterogeneous nature, usually diagnosed in childhood, with an elevated risk of infections such as otitis, skin infections, pneumonia, deep abscesses, and septicemia. Patients with SCN also have an increased risk of leukemia, and mutations in the ELANE and the HAX1 genes have been observed in those patients. This study was conducted to genetically screen six Iranian families with SCN who have at least one affected person. In the first step, all exons and intron boundaries of ELANE and HAX1 genes were sequenced in probands. Cases with no pathogenic mutations were tested through whole-exome sequencing (WES). Analysis showed five different variants in ELANE (c.377 C>T), HAX1 (c.130_131 insA), HYOU1 (c.69 G>C and c.2744 G>A) and SHOC2 (c.4 A>G) genes in four families. We found that two out of six families had mutations in ELANE and HAX1 genes. Moreover, we found two novel mutations at the HYOU1 gene that had not previously been reported, as well as a pathogenic mutation at SHOC2 with multiple phenotypes, that will contribute to determining the genetic basis for SCN. Our study revealed that WES could help diagnose SCN, improve the classification of neutropenia, and rule out other immunodeficiencies such as autoimmune neutropenia, primary immunodeficiency diseases, and inherited bone marrow failure syndromes. https://ijaai.tums.ac.ir/index.php/ijaai/article/view/3493ELANE proteinHAX1 proteinHYOU1 proteinSevere congenital neutropeniaSHOC2 proteinWhole exome sequencing |
| spellingShingle | Fatemeh Arab Nima Rezaei Forough Taheri Hamideh Kouhpeikar Elham Rayzan Mona Mirbeyk Davood Zare‐Abdollahi Mohsen Ghadami The Clinical and Molecular Assessment of Iranian Families with Severe Congenital Neutropenia, Identification of HYOU1 and SHOC2 as Potential Novel Gene Defects Iranian Journal of Allergy, Asthma and Immunology ELANE protein HAX1 protein HYOU1 protein Severe congenital neutropenia SHOC2 protein Whole exome sequencing |
| title | The Clinical and Molecular Assessment of Iranian Families with Severe Congenital Neutropenia, Identification of HYOU1 and SHOC2 as Potential Novel Gene Defects |
| title_full | The Clinical and Molecular Assessment of Iranian Families with Severe Congenital Neutropenia, Identification of HYOU1 and SHOC2 as Potential Novel Gene Defects |
| title_fullStr | The Clinical and Molecular Assessment of Iranian Families with Severe Congenital Neutropenia, Identification of HYOU1 and SHOC2 as Potential Novel Gene Defects |
| title_full_unstemmed | The Clinical and Molecular Assessment of Iranian Families with Severe Congenital Neutropenia, Identification of HYOU1 and SHOC2 as Potential Novel Gene Defects |
| title_short | The Clinical and Molecular Assessment of Iranian Families with Severe Congenital Neutropenia, Identification of HYOU1 and SHOC2 as Potential Novel Gene Defects |
| title_sort | clinical and molecular assessment of iranian families with severe congenital neutropenia identification of hyou1 and shoc2 as potential novel gene defects |
| topic | ELANE protein HAX1 protein HYOU1 protein Severe congenital neutropenia SHOC2 protein Whole exome sequencing |
| url | https://ijaai.tums.ac.ir/index.php/ijaai/article/view/3493 |
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