Abstract
INTRODUCTION: Molecular analysis of red cell disorders has revolutionized diagnosis, however, there remain challenges. MAIN SYMPTOMS: This patient presented with hemolytic anemia in the newborn period. He required chronic transfusions to maintain his hemoglobin level until 6 years of age. A splenectomy was performed at 3 years of age. MAIN DIAGNOSES: Using whole genome sequencing, we were able to identify a duplication upstream of the red cell promoter of HK1. Long-read RNA sequencing established aberrant expression off of this promoter. CONCLUSIONS: These non-coding variants remain challenging to identify. His promoter duplication may have a founder effect in South Asia.