Aims Congenital 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 methods Twenty 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.
Results Six 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’.
Conclusion This is the largest series of sideroblastic anaemia cases with molecular characterisation from the Indian subcontinent.
- anemia, sideroblastic
- genetic diseases, inborn
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Handling editor Mary Frances McMullin.
Contributors ESE and NR conceived the study. NR, ES, RA and SS designed and performed the tests. UK, AK, FNA and BG provided clinical input. NR wrote the manuscript. ESE, UK, RVS and BG reviewed the manuscript.
Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
Competing interests None declared.
Patient consent for publication Not required.
Ethics approval The study was approved by the Institutional Review Board.
Provenance and peer review Not commissioned; internally peer reviewed.
Data availability statement Data sets generated during the study are available in the published article and supplementary data or available at request from the corresponding author.
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