Diamond-Blackfan Anemia Confirmed by RPS19 Gene Mutation Analysis: A Case Study and Literature Review of Korean Patients
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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. (Korean J Lab Med 2010;30:249-54)
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. (Korean J Lab Med 2010;30:249-54)
참고문헌 (32)
- Diamond LK, "Hypoplastic anemia", Am J Dis Child, 56, pp.464~467 (1938)
- Campagnoli MF, "Molecular basis of Diamond-Blackfan anemia: new findings from the Italian registry and a review of the literature", Haematologica, 89, pp.480~489 (2004)
- Diamond LK, "Congenital hypoplastic anemia", Adv Pediatr, 22, pp.349~378 (1976)
- Vlachos A, "Diagnosing and treating Diamond Blackfan anaemia: results of an international clinical consensus conference", Br J Haematol, 142, pp.859~876 (2008)
- Orfali KA, "Diamond Blackfan anaemia in the UK: clinical and genetic heterogeneity", Br J Haematol, 125, pp.243~252 (2004)
- Campagnoli MF, "RPS19 mutations in patients with Diamond-Blackfan anemia", Hum Mutat, 29, pp.911~920 (2008)
- 李英永, "Congenital hypoplastic anemia의 1例", 소아과, 3, pp.66~70 (1962)
- 愼埰範, "先天性 低形成性貧血의 1例", 대한의학협회지, 9, pp.531~535 (1966)
- 박성원, "先天性 形成不全性 貧血", 대한혈액학회잡지, 9, pp.19~25 (1974)
- 李貴蘭, "Congenital hypoplastic anemia의1例", 소아과, 16, pp.73~77 (1975)
- 김광평, "Congenital pure red cell anemia 1예", 대한혈액학회잡지, 11, pp.39~45 (1976)
- 김동수, "Congenital hypoplastic anemia의 1예", 소아과, 23, pp.771~775 (1980)
- 이명현, "Congenital hypoplastic anemia의1예", 최신의학, 25, pp.31~35 (1982)
- 우영종, "Congenital hypoplastic anemia의1례", 소아과, 26, pp.188~192 (1983)
- 정현기, "Congenital hypoplastic anemia의 1례", 소아과, 26, pp.279~283 (1983)
- 변종인, "Congenital hypoplastic anemia의 1례", 최신의학, 27, pp.121~125 (1984)
- 이세진, "선천성재생불량성빈혈의1례", 소아과, 28, pp.61~64 (1985)
- 권희정, "선천성 저형성성 빈혈의 3예", 소아과, 28, pp.89~95 (1985)
- 황창희, "Congenital hypoplastic anemia 1예", 대한혈액학회지, 24, pp.187~193 (1989)
- 이재욱, "Congenital hypoplastic anemia 1례", 소아과, 32, pp.724~729 (1989)
- 김기호, "Congenital hypoplastic anemia 치험1례", 경북의대지, 30, pp.79~85 (1989)
- 강호원, "Congenital hypoplastic anemia 1례", 소아과, 33, pp.416~421 (1990)
- 이정명, "선천성형성부전성 빈혈 1예", 대한임상병리학회지, 14, pp.135~141 (1994)
- 손영준, "Diamond-Blackfan 빈혈: 6예 장기간 추적관찰보고", Korean Journal of Pediatrics, 51(11), pp.1211~1216 (2008), 대한소아과학회
- Lipton JM, "Improving clinical care and elucidating the pathophysiology of Diamond Blackfan anemia:an update from the Diamond Blackfan Anemia Registry", Pediatr Blood Cancer, 46, pp.558~564 (2006)
- Chen S, "Diamond-blackfan anemia and growth status: the French registry", J Pediatr, 147, pp.669~673 (2005)
- Bessler M, "Inherited bone marrow failure syndromes associated with isolated cytopenias. In: Orkin SH, Nathan DG, et al. eds. Nathan and Oski’s hematology of infancy and childhood. 7th ed", pp.351~360 (2009), Saunders Elsevier
- Liu JM, "Ribosomes and marrow failure: coincidental association or molecular paradigm?", Blood, 107, pp.4583~4588 (2006)
- Proust A, "Ten novel Diamond-Blackfan anemia mutations and three polymorphisms within the rps19 gene", Hematol J, 4, pp.132~136 (2003)
- Ramenghi U, "Diamond-Blackfan anemia: report of seven further mutations in the RPS19 gene and evidence of mutation heterogeneity in the Italian population", Blood Cells Mol Dis, 26, pp.417~422 (2000)
- Willig TN, "Mutations in ribosomal protein S19 gene and Diamond Blackfan anemia: wide variations in phenotypic expression", Blood, 94, pp.4294~4306 (1999)
- Kerem E, "Pharmacological induction of CFTR function in patients with cystic fibrosis: mutation-specific therapy", Pediatr Pulmonol, 40, pp.183~196 (2005)