Clinical Exome Sequencing Reveals Novel Mutations in SPTB Gene Associated with Hereditary Spherocytosis in Patients with Suspected Congenital Hemolytic Anemia

Abstract

Congenital hemolytic anemia (CHA) is defined as the premature destruction of red blood cells (RBC) due to congenital or acquired defects. The hereditary form of hemolytic anemia can be divided into hemoglobinopathies, membranopathies, and enzymopathies. Hereditary spherocytosis (HS) is the most common inherited RBC membranopathy leading to congenital hemolytic anemia. To date; five genes have been associated with HS coding for cytoskeleton and transmembrane proteins, those genes are SPTB, SLC4A1, EPB42, ANK1, and SPTA1. Due to genetic heterogeneity, clinical exome sequencing (CES) was performed on four unrelated Moroccan patients referred for CHA investigation. Sanger sequencing and qPCR were performed to confirm CES results and to study the de novo character of identified variants. The molecular analysis revealed 3 novel mutations and one previously reported pathogenic variant of the SPTB gene confirming the diagnosis of HS in the four patients. Hereditary spherocytosis anemia is a genetically heterogenous disease which could be misdiagnosed clinically. The introduction of novel sequencing technologies can facilitate accurate genetic diagnosis, allowing an adapted care of the patient and his family.

Keywords:

• Congenital hemolytic anemia
• HS
• moroccan
• SPTB
• NGS

Acknowledgment

The authors thank patients and their parents for their participation in this study.

Disclosure statement

The authors declare that they have no conflict of interest.

Ethics approval and consent to participate

All genetic testing in this study was performed after consent from the patients and/or their parents.

Data availability statement

Data available on request from the authors.

Additional information

Funding

The author(s) reported there is no funding associated with the work featured in this article.