Novel Frameshift Variant (C.409dupg) In Slc25a38 Is A Common Cause Of Congenital Sideroblastic Anaemia In The Indian Subcontinent

AimsCongenital sideroblastic anaemias (CSAs) are a group of rare disorders with the presence of ring sideroblasts in the bone marrow. Pathogenic variants are inherited in an autosomal recessive/X-linked fashion. The study was aimed at characterising the spectrum of mutations in SLC25A38 and ALAS2 genes in sideroblastic anaemia patients, exploring the genotype-phenotype correlation and identifying the haplotype associated with any recurrent mutation.Patients and methodsTwenty probable CSA patients were retrospectively analysed for genetic variants in ALAS2 and SLC25A38 genes by direct bidirectional sequencing. Real-time PCR was used to quantify gene expression in a case with promoter region variant in ALAS2. Three single nucleotide polymorphisms were used to establish the haplotype associated with a recurrent variant in the SLC25A38 gene.ResultsSix patients had causative variants in ALAS2 (30%) and 11 had variants in SLC25A38 (55%). The ALAS2 mutated cases presented at a significantly later age than the SLC25A38 cases. A frameshift variant in SLC25A38 (c.409dupG) was identified in six unrelated patients and was a common variant in our population exhibiting 'founder effect'.ConclusionThis is the largest series of sideroblastic anaemia cases with molecular characterisation from the Indian subcontinent.