Molecular Diagnosis of Congenital Sideroblastic Anemia in Iranian Families

Sideroblastic anemia is a rare hematological disorder characterized by ringsideroblasts. These rings are caused by pathogenic deposition of iron inmitochondria that hasn’t been incorporated into hemoglobin in erythroblasts andare detectable by Prussian blue staining of bone marrow aspirate smear inerythroblasts. Sideroblastic anemia could be acquired or inherited and dependingon the gene involved, it could be syndromic, nonsyndromic, autosomal or X-linkedand the severity of anemia, the age of onset, prognosis and response to drugs orclinical interventions depend on the causative gene involved. Mutations in severalgenes have been shown to cause various subtypes of this disease. Therefore,genetic diagnosis is essential in accurate identification and management ofsideroblastic anemia.Here, we used whole exome sequencing to identify the cause of congenital,microcytic hypochromic severe anemia in four unrelated Iranian families, with atleast one affected member suspected to have rare types of hereditary anemias. Twonovel frameshift deletions and one previously reported missense mutation inSLC۲۵A۳۸ gene were identified in the probands. This gene is a member of themitochondrial carrier family, which is involved in erythropoiesis and is requiredfor the heme biosynthesis. Mutations in this gene are reported in cases withautosomal recessive congenital sideroblastic anemia, which unlike the X-linkedsub-type do not respond to pyridoxine (vitamin B۶). Diagnosis of congenitalsideroblastic anemia in affected individuals was confirmed by further family studies and detection of ring sideroblasts in bone marrow examination of the probands.

کلیدواژه ها:

rare blood disorders ، congenital sideroblastic anemia ، SLC۲۵A۳۸ ، microcytic hypochromic hemolytic anemia ، whole exome sequencing