Abstract
Diamond–Blackfan anemia (DBA) is a pure red cell aplasia that arises from defective ribosomal proteins (RPs). Patients with this rare ribosomopathy present with neonatal anemia and occasional dysmorphism. Clinical heterogeneity and clusters of causative RP genes hamper the diagnosis and perinatal management. We report three mother-and-child pairs of anemia who were finally diagnosed by whole-exome sequencing. Each pair showed distinct disease severity and response to anemia treatment. Only one mother had the diagnostic dysmorphism, including short stature, webbed neck, and thenar hypoplasia. This mother had a frame-shift mutation of RPL11 (exon 3, c.58_59del). Her infant showed transient neonatal anemia, but had no mutations of RP genes. The other mother–child pairs had a missense mutation of RPS19 (exon 4, c.185G>A), and a splicing error of RPS7 (exon 3, c.76-1G>T), respectively. Other than the reported mutations, there were no variants in genes significantly associated with anemia. Our results suggested that whole-exome sequencing (WES) is effective for achieving a prompt and correct diagnosis of human ribosomopathy.
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Abbreviations
- WES:
-
whole-exome sequencing
- DBA:
-
Diamond–Blackfan anemia
- RP:
-
ribosomal protein
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Acknowledgements
We thank Dr. Yoshihiro Azuma (Department of Pediatrics, Yamaguchi University Graduate School of Medicine, Ube, Japan) and Prof. Yukio Tanizawa (Third Department of Internal Medicine, Yamaguchi University Graduate School of Medicine, Ube, Japan) for the clinical management and useful suggestions. We also thank Dr. Brian Quinn (Editor-in-Chief. Japan Medical Communication) for editing the manuscript. This work was supported by a “Research on Measures for Intractable Diseases” Project (H23-012): matching fund subsidy from the Ministry of Health Labour and Welfare of Japan, and Grants-in-Aid for Scientific Research (Research on Intractable Diseases) from the Ministry of Health, Labour and Welfare of Japan (H23-029).
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Ichimura, T., Yoshida, K., Okuno, Y. et al. Diagnostic challenge of Diamond–Blackfan anemia in mothers and children by whole-exome sequencing. Int J Hematol 105, 515–520 (2017). https://doi.org/10.1007/s12185-016-2151-7
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DOI: https://doi.org/10.1007/s12185-016-2151-7