Korean J Lab Med.  2010 Jun;30(3):249-254. 10.3343/kjlm.2010.30.3.249.

Diamond-Blackfan Anemia Confirmed by RPS19 Gene Mutation Analysis: A Case Study and Literature Review of Korean Patients

• Chae H
• Park J
• Kim M
• Lim J
• Kim Y
• Han K
• Lee J
• Chung NG
• Cho B
• Kim HK

• KMID: 1781623
• DOI: http://doi.org/10.3343/kjlm.2010.30.3.249

Abstract

Diamond-Blackfan anemia (DBA) is a rare congenital erythroid hypoplastic anemia that usually presents early in infancy and is inherited in up to 45% of cases. It is characterized by red cell aplasia, congenital anomalies, and a predisposition to cancer. Corticosteroids and red blood cell transfusions are the mainstays of therapy. We describe a case of 3-month-old infant who presented with severe anemia, elevated levels of HbF and adenosine deaminase and bilateral hydronephrosis, who was later confirmed as DBA by mutation analysis using the direct sequencing method. Direct sequencing analysis of RPS19 gene was performed with both cDNA and genomic DNA extracted from peripheral blood and a c.3G>A point mutation of exon 2 resulting in p.Met1Ile was identified in this patient. The patient showed an inadequate response to steroid therapy and a partial response to RBC transfusion with a follow-up Hb level of 8.3 g/dL on her last visit to the outpatient clinic. DBA is a genetically and phenotypically heterogeneous disease, and we have reviewed the clinical characteristics of 25 Korean patients thus far reported in the literature. To our knowledge, this is the first case of DBA confirmed by mutation analysis in Korea, and mutation identification using molecular method is recommended for confirmation of this genetically and phenotypically heterogeneous disease.

Keyword

Diamond-Blackfan anemia; Sequencing analysis; RPS19

MeSH Terms

Anemia, Diamond-Blackfan/*diagnosis/genetics/therapy
Asian Continental Ancestry Group/*genetics
Bone Marrow/pathology
Erythrocyte Transfusion
Exons
Humans
Infant
Point Mutation
Republic of Korea
Ribosomal Proteins/*genetics
Sequence Analysis, DNA

Figure

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  Fig. 1. Bone marrow aspirate (A, Wright-Giemsa stain, ×400) and bone marrow biopsy (B, hematoxylin and eosin stain, ×200) showing normal cellularity and characteristic paucity of erythroid precursors. The other lineages show no evident abnormalities.

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  Fig. 2. (A) Genes associated with DBA. (B) The gene structure of RPS19. (C) Direct sequencing analysis of RPS19. The G to A substitution is expected to produce a methionine to isoleucine substitution of the initiation codon. Abbreviation: DBA, Diamond-Blackfan anemia.

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