X‐Linked Sideroblastic Anaemia Caused by Intronic ALAS2 Variant Resulting in Highly Variable Expressive Phenotype in Male Siblings, a Case Report
ABSTRACT X‐linked sideroblastic anaemia (XLSA) is a rare hereditary disorder caused by mutations in the ALAS2 gene, essential for haem biosynthesis. We report two male siblings, the first of whom developed severe microcytic hypochromic anaemia requiring regular transfusions, iron chelation and an al...
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| Format: | Article |
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Wiley
2025-06-01
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| Series: | eJHaem |
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| Online Access: | https://doi.org/10.1002/jha2.70060 |
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| author | James O'Connor Niall Mannion Caoimhe McKenna Kerrie Sweeney Aaron Niblock |
| author_facet | James O'Connor Niall Mannion Caoimhe McKenna Kerrie Sweeney Aaron Niblock |
| author_sort | James O'Connor |
| collection | DOAJ |
| description | ABSTRACT X‐linked sideroblastic anaemia (XLSA) is a rare hereditary disorder caused by mutations in the ALAS2 gene, essential for haem biosynthesis. We report two male siblings, the first of whom developed severe microcytic hypochromic anaemia requiring regular transfusions, iron chelation and an allogeneic bone marrow transplant, while his brother displayed only mild microcytic hypochromic indices without anaemia. Initial genetic screening did not identify a pathogenic variant. However, duo exome sequencing later revealed an intronic ALAS2 mutation, initially categorised as of uncertain significance and subsequently reclassified as pathogenic. This case underscores the diagnostic challenges posed by intronic mutations and the highly variable expressivity of XLSA, even among siblings. Trial Registration: The authors have confirmed clinical trial registration is not needed for this submission. |
| format | Article |
| id | doaj-art-87ea0c8303d54973bdb57a89a1753a71 |
| institution | DOAJ |
| issn | 2688-6146 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Wiley |
| record_format | Article |
| series | eJHaem |
| spelling | doaj-art-87ea0c8303d54973bdb57a89a1753a712025-08-20T03:16:16ZengWileyeJHaem2688-61462025-06-0163n/an/a10.1002/jha2.70060X‐Linked Sideroblastic Anaemia Caused by Intronic ALAS2 Variant Resulting in Highly Variable Expressive Phenotype in Male Siblings, a Case ReportJames O'Connor0Niall Mannion1Caoimhe McKenna2Kerrie Sweeney3Aaron Niblock4School of Medicine Ulster University Londonderry UKSchool of Medicine Ulster University Londonderry UKNorthern Ireland Regional Genetics Laboratory Belfast UKHaematology department Antrim Area Hospital Antrim UKSchool of Medicine Ulster University Londonderry UKABSTRACT X‐linked sideroblastic anaemia (XLSA) is a rare hereditary disorder caused by mutations in the ALAS2 gene, essential for haem biosynthesis. We report two male siblings, the first of whom developed severe microcytic hypochromic anaemia requiring regular transfusions, iron chelation and an allogeneic bone marrow transplant, while his brother displayed only mild microcytic hypochromic indices without anaemia. Initial genetic screening did not identify a pathogenic variant. However, duo exome sequencing later revealed an intronic ALAS2 mutation, initially categorised as of uncertain significance and subsequently reclassified as pathogenic. This case underscores the diagnostic challenges posed by intronic mutations and the highly variable expressivity of XLSA, even among siblings. Trial Registration: The authors have confirmed clinical trial registration is not needed for this submission.https://doi.org/10.1002/jha2.70060ALAS2case reportcongenital sideroblastic anaemiahaematopoietic stem cell transplantationvariable expressivityX‐linked sideroblastic anaemia |
| spellingShingle | James O'Connor Niall Mannion Caoimhe McKenna Kerrie Sweeney Aaron Niblock X‐Linked Sideroblastic Anaemia Caused by Intronic ALAS2 Variant Resulting in Highly Variable Expressive Phenotype in Male Siblings, a Case Report eJHaem ALAS2 case report congenital sideroblastic anaemia haematopoietic stem cell transplantation variable expressivity X‐linked sideroblastic anaemia |
| title | X‐Linked Sideroblastic Anaemia Caused by Intronic ALAS2 Variant Resulting in Highly Variable Expressive Phenotype in Male Siblings, a Case Report |
| title_full | X‐Linked Sideroblastic Anaemia Caused by Intronic ALAS2 Variant Resulting in Highly Variable Expressive Phenotype in Male Siblings, a Case Report |
| title_fullStr | X‐Linked Sideroblastic Anaemia Caused by Intronic ALAS2 Variant Resulting in Highly Variable Expressive Phenotype in Male Siblings, a Case Report |
| title_full_unstemmed | X‐Linked Sideroblastic Anaemia Caused by Intronic ALAS2 Variant Resulting in Highly Variable Expressive Phenotype in Male Siblings, a Case Report |
| title_short | X‐Linked Sideroblastic Anaemia Caused by Intronic ALAS2 Variant Resulting in Highly Variable Expressive Phenotype in Male Siblings, a Case Report |
| title_sort | x linked sideroblastic anaemia caused by intronic alas2 variant resulting in highly variable expressive phenotype in male siblings a case report |
| topic | ALAS2 case report congenital sideroblastic anaemia haematopoietic stem cell transplantation variable expressivity X‐linked sideroblastic anaemia |
| url | https://doi.org/10.1002/jha2.70060 |
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