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To the Editor: Congenital dyserythropoietic anemia (CDA) type II is the most common among other types of CDAs. It is inherited in an autosomal recessive pattern and caused due to mutations in the SEC23B gene [1]. Patients show moderate to severe anemia, variable transfusion requirement, icterus, pallor, hepatosplenomegaly, morphological abnormalities in the bone marrow. The gold standard for diagnosis is light and electron microscopic observation of bone marrow [2]. The molecular characterization gives a confirmed diagnosis. There are many reports of CDAII globally. However, only a few patients have been reported in the Indian population based on bone marrow morphological analysis [3].
The objective of this study was to investigate the cause of severe anemia, hepatosplenomegaly, icterus, recurrent jaundice in reference to CDA. The identification of mutation causing CDAII was performed using targeted next-generation sequencing, Sanger sequencing, and rapid detection using newly developed high-resolution melting (HRM) curve analysis. Sequence-related melt curves are generated using HRM and difference plots generated with the help of melt curves can reveal differences in the genotype [4]. We have standardized the use of HRM for the detection of common mutations causing CDAII in the Indian population. This assay was performed using Applied Biosystems StepOneTM Real-Time PCR System.
Twelve CDAII patients were identified with anemia, icterus, pallor, hepatosplenomegaly and indirect hyperbilirubinemia. Sanger sequencing showed c.1385 A>G, p. Tyr462Cys mutation in all patients. A difference plot using HRM analysis showed a prominent peak of homozygous mutation p.Tyr462Cys in patients and heterozygous mutation in parents. We describe the high prevalence of c.1385 A>G mutation in the SEC23B gene in Indian CDAII patients. The application of HRM analysis for the identification of p.Tyr462Cys is a very simple, accurate, and cost-effective method for screening this mutation in the Indian population. The introduction of this technique is likely to impact on studying the prevalence of CDA.
References
Bianchi P, Fermo E, Vercellati C, et al. Congenital dyserythropoietic anemia type II (CDAII) is caused by mutations in the SEC23B gene. Hum Mutat. 2009;30:1292–8.
Heimpel H, Kellermann K, Neuschwander N, Högel J, Schwarz K. The morphological diagnosis of congenital dyserythropoietic anemia: Results of a quantitative analysis of peripheral blood and bone marrow cells. Haematologica. 2010;95:1034.
Marwaha RK, Bansal D, Trehan A, Garewal G, Marwaha N. Congenital dyserythropoieticanemia: Clinical and hematological profile. Indian Pediatr. 2003;40:551–5.
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Funding
This study was performed with the financial support of the Indian Council of Medical Research New Delhi (ICMR Project NO. 54/2/2020-HUM/BMS). The funding body played no role in the design of the study and collection, analysis, and interpretation of data and in writing the manuscript.
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Saptarshi, A.N., More, T.A., Dongerdiye, R. et al. Congenital Dyserythropoietic Anemia Type II: High Prevalence of c.1385A>G, (p.Tyr462Cys) Mutation in the Indian Population. Indian J Pediatr 90, 840 (2023). https://doi.org/10.1007/s12098-023-04662-1
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DOI: https://doi.org/10.1007/s12098-023-04662-1