Whole-Exome Sequencing Revealed a Pathogenic Nonsense Variant in the SLC19A2 Gene in an Iranian Family with Thiamine-Responsive Megaloblastic Anemia

Objective Solute carrier family 19 member 2 (SLC19A2, OMIM *603941) encodes thiamine human transporter 1 (THTR-1), which contributes to bringing thiamine (vitamin B1) into cells. Mutations in SLC19A2 lead to a rare recessive genetic disorder termed thiamine-responsive megaloblastic anemia (TRMA) syndrome. Methods An Iranian family with TRMA was investigated by whole-exome sequencing (WES) to determine the genetic cause(s) of the disease. Accordingly, SLC19A2 genetic variants were gathered through literature analysis. Results WES recognized a known pathogenic variant, c.697C > T (p. Q233X), within exon 2 of SLC19A2 (NM_006996). Subsequently, the proband’s parents and sister were confirmed as heterozygous carriers of the identified variant. Conclusion The diagnostic utility and affordability of WES were confirmed as the first approach for the genetic testing of TRMA to verify the diagnosis. This analysis can be used to guide future prenatal diagnoses and determine the consequences in the other family members.