Exome sequencing results in successful diagnosis and treatment of a severe congenital anemia


Whole-exome sequencing is increasingly used for diagnosis and identification of appropriate therapies in patients. Here, we present the case of a 3-yr-old male with a lifelong and severe transfusion-dependent anemia of unclear etiology, despite an extensive clinical workup. Given the difficulty of making the diagnosis and the potential side effects from performing interventions in patients with a congenital anemia of unknown etiology, we opted to perform whole-exome sequencing on the patient and his parents. This resulted in the identification of homozygous loss-of-function mutations in the EPB41 gene, encoding erythrocyte protein band 4.1, which therefore causes a rare and severe form of hereditary elliptocytosis in the patient. Based on prior clinical experience in similar patients, a surgical splenectomy was performed that resulted in subsequent transfusion independence in the patient. This case illustrates how whole-exome sequencing can lead to accurate diagnoses (and exclusion of diagnoses where interventions, such as splenectomy, would be contraindicated), thereby resulting in appropriate and successful therapeutic intervention-a major goal of precision medicine.

DOI: 10.1101/mcs.a000885

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@inproceedings{Lacy2016ExomeSR, title={Exome sequencing results in successful diagnosis and treatment of a severe congenital anemia}, author={Jessica Lacy and Jacob C . Ulirsch and Rachael F. Grace and Meghan C. Towne and John E. S. Hale and Narla Mohandas and Samuel E. Lux and Pankaj B Agrawal and Vijay G Sankaran}, booktitle={Cold Spring Harbor molecular case studies}, year={2016} }