Case report: A novel 11-bp deletion in exon 11 causing a frameshift in the C-terminal of the ALAS2 gene leading to X-linked sideroblastic anemia—a family study
X-linked sideroblastic anemia (XLSA) (MIM 300752) is the most common genetic form of sideroblastic anemia, a heterogeneous group of disorders characterized by iron deposits in the mitochondria of erythroid precursors. It is due to mutations of the erythroid-specific enzyme ALAS2, the first enzyme of...
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Frontiers Media S.A.
2025-02-01
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| author | Salam Al kindi Salam Al kindi Altaf Al-Mamari Shoaib Al-Zadjali Mohamed Al-Rawahi Ali Al Madhani Anil V. Pathare |
| author_facet | Salam Al kindi Salam Al kindi Altaf Al-Mamari Shoaib Al-Zadjali Mohamed Al-Rawahi Ali Al Madhani Anil V. Pathare |
| author_sort | Salam Al kindi |
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| description | X-linked sideroblastic anemia (XLSA) (MIM 300752) is the most common genetic form of sideroblastic anemia, a heterogeneous group of disorders characterized by iron deposits in the mitochondria of erythroid precursors. It is due to mutations of the erythroid-specific enzyme ALAS2, the first enzyme of the heme biosynthetic pathway. Herein, we report a novel 11-bp deletion in exon 11 leading to a frameshift in the C-terminal region of the ALAS2 gene with a non-functional longer polypeptide of 614 amino acids leading to a loss-of-function mutation manifested as an X-linked sideroblastic anemia phenotype. The proband was a 29-year-old man with moderately severe microcytic hypochromic anemia with splenomegaly and increased ring sideroblasts in the bone marrow with considerable iron overload. Sanger sequencing documented a missense mutation leading to a frameshift with an elongated polypeptide of 614 AA instead of the normal 587 AA protein c.1743_1753 del (p.Gln581Hisfs*35). This mutation affected the interaction with cofactor pyridoxal 5′-phosphate since the patient’s hemoglobin improved with oral administration of pyridoxine tablets. His iron overload also responded to sustained oral iron chelation therapy with deferasirox. The screening of the entire family’s kindred revealed that two other male siblings were also hemizygous for the same mutation with hypochromic microcytic anemia and tissue iron overload, whereas, three female siblings and their mother were heterozygous for the mutant allele. They did not have anemia or iron overload. |
| format | Article |
| id | doaj-art-b9db61ae28b74b0d9a26b92955b18e1a |
| institution | Kabale University |
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| language | English |
| publishDate | 2025-02-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Medicine |
| spelling | doaj-art-b9db61ae28b74b0d9a26b92955b18e1a2025-02-10T04:11:05ZengFrontiers Media S.A.Frontiers in Medicine2296-858X2025-02-011110.3389/fmed.2024.14528731452873Case report: A novel 11-bp deletion in exon 11 causing a frameshift in the C-terminal of the ALAS2 gene leading to X-linked sideroblastic anemia—a family studySalam Al kindi0Salam Al kindi1Altaf Al-Mamari2Shoaib Al-Zadjali3Mohamed Al-Rawahi4Ali Al Madhani5Anil V. Pathare6Department of Haematology, Sultan Qaboos University Hospital, Muscat, OmanCollege of Medicine & Health Sciences, Muscat, OmanDepartment of Medicine, Sohar Hospital, Sohar, OmanDepartment of Haematology, Sultan Qaboos University Hospital, Muscat, OmanDepartment of Haematology, Sultan Qaboos University Hospital, Muscat, OmanDepartment of Medicine, Sohar Hospital, Sohar, OmanDepartment of Haematology, Sultan Qaboos University Hospital, Muscat, OmanX-linked sideroblastic anemia (XLSA) (MIM 300752) is the most common genetic form of sideroblastic anemia, a heterogeneous group of disorders characterized by iron deposits in the mitochondria of erythroid precursors. It is due to mutations of the erythroid-specific enzyme ALAS2, the first enzyme of the heme biosynthetic pathway. Herein, we report a novel 11-bp deletion in exon 11 leading to a frameshift in the C-terminal region of the ALAS2 gene with a non-functional longer polypeptide of 614 amino acids leading to a loss-of-function mutation manifested as an X-linked sideroblastic anemia phenotype. The proband was a 29-year-old man with moderately severe microcytic hypochromic anemia with splenomegaly and increased ring sideroblasts in the bone marrow with considerable iron overload. Sanger sequencing documented a missense mutation leading to a frameshift with an elongated polypeptide of 614 AA instead of the normal 587 AA protein c.1743_1753 del (p.Gln581Hisfs*35). This mutation affected the interaction with cofactor pyridoxal 5′-phosphate since the patient’s hemoglobin improved with oral administration of pyridoxine tablets. His iron overload also responded to sustained oral iron chelation therapy with deferasirox. The screening of the entire family’s kindred revealed that two other male siblings were also hemizygous for the same mutation with hypochromic microcytic anemia and tissue iron overload, whereas, three female siblings and their mother were heterozygous for the mutant allele. They did not have anemia or iron overload.https://www.frontiersin.org/articles/10.3389/fmed.2024.1452873/fullsideroblastic anemiaXLSAX-linkedALAS2congenital |
| spellingShingle | Salam Al kindi Salam Al kindi Altaf Al-Mamari Shoaib Al-Zadjali Mohamed Al-Rawahi Ali Al Madhani Anil V. Pathare Case report: A novel 11-bp deletion in exon 11 causing a frameshift in the C-terminal of the ALAS2 gene leading to X-linked sideroblastic anemia—a family study Frontiers in Medicine sideroblastic anemia XLSA X-linked ALAS2 congenital |
| title | Case report: A novel 11-bp deletion in exon 11 causing a frameshift in the C-terminal of the ALAS2 gene leading to X-linked sideroblastic anemia—a family study |
| title_full | Case report: A novel 11-bp deletion in exon 11 causing a frameshift in the C-terminal of the ALAS2 gene leading to X-linked sideroblastic anemia—a family study |
| title_fullStr | Case report: A novel 11-bp deletion in exon 11 causing a frameshift in the C-terminal of the ALAS2 gene leading to X-linked sideroblastic anemia—a family study |
| title_full_unstemmed | Case report: A novel 11-bp deletion in exon 11 causing a frameshift in the C-terminal of the ALAS2 gene leading to X-linked sideroblastic anemia—a family study |
| title_short | Case report: A novel 11-bp deletion in exon 11 causing a frameshift in the C-terminal of the ALAS2 gene leading to X-linked sideroblastic anemia—a family study |
| title_sort | case report a novel 11 bp deletion in exon 11 causing a frameshift in the c terminal of the alas2 gene leading to x linked sideroblastic anemia a family study |
| topic | sideroblastic anemia XLSA X-linked ALAS2 congenital |
| url | https://www.frontiersin.org/articles/10.3389/fmed.2024.1452873/full |
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