1. Identification of a novel splice variant in SEC23B gene in a patient with concomitant presence of congenital dyserythropoietic anemia II and Gilbert’s syndrome
- Author
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Woori Jang, Dong Jun Ha, Chung Hyun Nahm, Jisun Park, Su Jin Kim, Ji-Eun Lee, and Yeonsook Moon
- Subjects
Congenital dyserythropoietic anemia II ,next generation sequencing ,SEC23B ,splicing defects ,Gilbert’s syndrome ,Diseases of the blood and blood-forming organs ,RC633-647.5 - Abstract
ABSTRACTBackground: Congenital dyserythropoietic anemia Ⅱ (CDA Ⅱ) is a rare inherited disorder of defective erythropoiesis caused by SEC23B gene mutation. CDA Ⅱ is often misdiagnosed as a more common type of clinically related anemia, or it remains undiagnosed due to phenotypic variability caused by the coexistence of inherited liver diseases, including Gilbert’s syndrome (GS) and hereditary hemochromatosis.Methods: We describe the case of a boy with genetically undetermined severe hemolytic anemia, hepatosplenomegaly, and gallstones whose diagnosis was achieved by targeted next generation sequencing.Results: Molecular analysis revealed a maternally inherited novel intronic variant and a paternally inherited missense variant, c.[994-3C > T];[1831C > T] in the SEC23B gene, confirming diagnosis of CDA Ⅱ. cDNA analysis verified that the splice acceptor site variant results in two mutant transcripts, one with an exon 9 skip and one in which exons 9 and 10 are deleted. SEC23B mRNA levels in the patient were lower than those in healthy controls. The patient was also homozygous for the UGT1A1*6 allele, consistent with GS.Conclusion: Identification of the novel splice variant in this study further expands the spectrum of known SEC23B gene mutations. Molecular genetic approaches can lead to accurate diagnosis and management of CDA Ⅱ patients, particularly for those with GS coexisting.
- Published
- 2024
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