A novel frameshift deletion in SLC25A38 and its role in mitochondrial dysfunction: A case study of sideroblastic anemia in a child from Iran

Sideroblastic anemia (SA) is a rare hematological condition characterized by the accumulation of iron in the mitochondria of erythroid precursor cells, resulting in the formation of sideroblastic rings. It occurs in both inherited and acquired forms. A prevalent subtype of congenital sideroblastic anemia (CSA) results from autosomal recessive mutations in the SLC25A38 gene. This investigation included a clinical and genetic evaluation of a family with a child diagnosed with pyridoxine-refractory SA. Whole Exome Sequencing (WES) was performed on the patient to detect the genetic variation. Afterwards, to examine segregation, Sanger sequencing of the related gene was conducted on the patient’s parents and the fetus of this family. On the other hand, the proband’s aunt and her husband, whose daughter died from symptoms similar to SA, were also evaluated for this variation. The next step involved molecular docking studies for the SLC25A38 protein pre- and post-variation. The WES analysis demonstrated the c.482_485del (p. Ile161ThrfsTer4) variant in the SLC25A38 gene, present in the probands as homozygotes and in the parents as heterozygotes. The chemical binds and stability of the protein in the mutant form was observed to be diminished in comparison to the wild form. This study enabled the reclassification of the SLC25A38: c.482_485del from likely pathogenic to pathogenic, which will significantly assist specialists in making decisions about this variant.