A novel variant in the SPTB gene underlying hereditary spherocytosis and a literature review of previous variants.
SPTB gene
Hereditary spherocytosis
Minigene
Novel variant
Journal
BMC medical genomics
ISSN: 1755-8794
Titre abrégé: BMC Med Genomics
Pays: England
ID NLM: 101319628
Informations de publication
Date de publication:
12 Aug 2024
12 Aug 2024
Historique:
received:
26
01
2024
accepted:
29
07
2024
medline:
13
8
2024
pubmed:
13
8
2024
entrez:
12
8
2024
Statut:
epublish
Résumé
Hereditary spherocytosis (HS, MIM#612641) is one of the most common hereditary hemolytic disorders. This study aimed to confirm a novel variant's pathogenicity and reveal a patient's genetic etiology. The clinical data of a patient with HS who underwent genetic sequencing at the Children's Hospital of Chongqing Medical University were reviewed retrospectively. In silico prediction and in vitro minigene splicing reporter system were then conducted on the detected variant to analyze its intramolecular impact. A summary of the literature related to HS due to SPTB gene variants was also presented. A novel variant (c.301-2 A > G) in the SPTB gene (NM_001024858.4) was identified in the proband. Using Sanger sequencing, we conclusively confirmed that the inheritance of the variant could not be traced to the biological parents. The in vitro minigene assay revealed three different transcripts derived from the c.301-2 A > G variant: r.301_474del, r.301_306delCCAAAG, and r.301-1_301-57ins. Through a literature review, patients with HS who had been genotypically validated were summarized and the SPTB gene variant profile was mapped. We identified a splicing variant of the SPTB gene, thus confirming its aberrant translation. The novel variant was the probable genetic etiology of the proband with HS. Our findings expanded the variant spectrum of the SPTB gene, thus improving the understanding of the associated hereditary hemolytic disorders from a clinical and molecular perspective and contributing to the foundation of genetic counseling and diagnosis.
Sections du résumé
BACKGROUND
BACKGROUND
Hereditary spherocytosis (HS, MIM#612641) is one of the most common hereditary hemolytic disorders. This study aimed to confirm a novel variant's pathogenicity and reveal a patient's genetic etiology.
METHODS
METHODS
The clinical data of a patient with HS who underwent genetic sequencing at the Children's Hospital of Chongqing Medical University were reviewed retrospectively. In silico prediction and in vitro minigene splicing reporter system were then conducted on the detected variant to analyze its intramolecular impact. A summary of the literature related to HS due to SPTB gene variants was also presented.
RESULTS
RESULTS
A novel variant (c.301-2 A > G) in the SPTB gene (NM_001024858.4) was identified in the proband. Using Sanger sequencing, we conclusively confirmed that the inheritance of the variant could not be traced to the biological parents. The in vitro minigene assay revealed three different transcripts derived from the c.301-2 A > G variant: r.301_474del, r.301_306delCCAAAG, and r.301-1_301-57ins. Through a literature review, patients with HS who had been genotypically validated were summarized and the SPTB gene variant profile was mapped.
CONCLUSION
CONCLUSIONS
We identified a splicing variant of the SPTB gene, thus confirming its aberrant translation. The novel variant was the probable genetic etiology of the proband with HS. Our findings expanded the variant spectrum of the SPTB gene, thus improving the understanding of the associated hereditary hemolytic disorders from a clinical and molecular perspective and contributing to the foundation of genetic counseling and diagnosis.
Identifiants
pubmed: 39135028
doi: 10.1186/s12920-024-01973-w
pii: 10.1186/s12920-024-01973-w
doi:
Substances chimiques
SPTB protein, human
0
Spectrin
12634-43-4
Types de publication
Journal Article
Case Reports
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
206Subventions
Organisme : Public Welfare Project for Rare Blood Disorders in the field of Hematology in China
ID : xyxthjb-2023-006
Organisme : Public Welfare Project for Rare Blood Disorders in the field of Hematology in China
ID : xyxthjb-2023-006
Organisme : Public Welfare Project for Rare Blood Disorders in the field of Hematology in China
ID : xyxthjb-2023-006
Organisme : Public Welfare Project for Rare Blood Disorders in the field of Hematology in China
ID : xyxthjb-2023-006
Organisme : Public Welfare Project for Rare Blood Disorders in the field of Hematology in China
ID : xyxthjb-2023-006
Organisme : Public Welfare Project for Rare Blood Disorders in the field of Hematology in China
ID : xyxthjb-2023-006
Organisme : Public Welfare Project for Rare Blood Disorders in the field of Hematology in China
ID : xyxthjb-2023-006
Organisme : Public Welfare Project for Rare Blood Disorders in the field of Hematology in China
ID : xyxthjb-2023-006
Organisme : Public Welfare Project for Rare Blood Disorders in the field of Hematology in China
ID : xyxthjb-2023-006
Informations de copyright
© 2024. The Author(s).
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