An Unexpectedly High Frequency of Sptb Gene Mutation (SPTB exon 29: c.6055T>C (p.Ser2019Pro; Spectrin Thai)) with a Single Origin in Thailand Suggesting a New Model of Red Blood Cell Trait Against Malarial Pressure

Mutations in SPTB gene coding β-spectrin can lead to congenital hemolytic anemia (HA) or red cell membranopathy. Most patients presented with mild to moderate HA with either spherocytes or ovalo-elliptocytes. Only one report in the literature described a family with non-immune hydrops fetalis (HF) due to homozygous SPTB: c.6055T>C (p.Ser2019Pro). Recently, we have identified the second patient presented with HF in Thailand with the same genotypes through genomic approach. This finding has driven extensive study to determine the impact of SPTB mutation in our cohort of unexplained HA and HF.From 107,947 live births at our center between 2005 and 2016, 83 non-immune HF were identified. Nineteen cases from 42 unexplained HF (45%) had FFPE DNA available from autopsy (Fig 1). In addition, 7 patients who were transfusion dependent anemia due to unknown cause were recruited. These were subjects of our Whole Exome Analysis (WES) using Illumina HiSeq4000 capturing by SureSelect V5 plus UTR covering 21,522 genes. Moreover, we studied WES in 120 Thai individuals without anemia as controls. Surprisingly, 6 out of 26 patients (23%) were homozygous SPTB: c.6055T>C and none in controls. We confirmed this finding by direct genomic Sanger sequencing and set up a PCR-RFLP to detect this further in other cohorts. Interestingly, we found additional 13 heterozygotes of this mutation in our thalassemia patients (1 in 361) and general population (12 in 2,576) (Fig 1) making an unexpected...
Source: Blood - Category: Hematology Authors: Tags: 101. Red Cells and Erythropoiesis, Structure and Function, Metabolism, and Survival, Excluding Iron: Poster II Source Type: research