A novel mutation in SPTA1 identified by whole exome sequencing in a Chinese family for hereditary elliptocytosis presenting with hyperbilirubinemia A case report

Rationale: Hereditary elliptocytosis is an inherited disorder characterized by the elliptical red blood cells (RBCs) on the peripheral blood smear and related hemolysis, mainly results from a heterozygous mutation in the genes that encode protein 4.1, alpha-spectrin, beta-spectrin. Mutations of SPTA1 are the most common. Patient concerns: A 21-year-old female presented with left epigastric pain and jaundice with numerous elliptical RBCs on blood film. The family history review discovered jaundice in her sibling. Diagnosis: A novel heterozygous mutation of SPTA1 was detected in the proband, her brother and father, c.7220_7221del:p. Tyr2407* in exon 52. Bioinformatics analysis indicated that this mutation was likely pathogenic and results in early termination of transcription and production of defective protein. Interventions: The proband underwent splenectomy and cholecystectomy due to symptomatic splenomegaly and gallstone. Outcomes: After surgery, the bilirubin levels decreased to normal (i.e., total bilirubin 16.4mmol/L; indirect bilirubin 12.3mmol/L), and the pain and uncomfortableness in the upper abdomen relieved completely. Lessons: We suggest that simultaneous whole exome sequencing of causative genes of all family members is a useful strategy to identify pathogenetic mutations for hereditary RBC membrane disorders, mainly in cases with an ambiguous phenotype.