Diamond-Blackfan Anemia 9

Watchlist

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Retrieved

2019-09-22

Source

Omim

Trials

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Genes

GATA1, RPS19, RPS24, RPS17, ADA2, RPL27, RPL26, RPL15, RPS27, RPS29, RPL35, TSR2, RPL18, RPL11, RPL5, RPS28, RPL35A, RPS7, RPS26, EPO, RPS10, RPL9, RPL31, RPS27A, RPL19, RPL36, RPL13, RPS15A, RPL23, RPS15, FLVCR1, TP53, RPSA, IQCG, DIPK1A, CD34, RPS14, LOH19CR1, ADA, KITLG, THPO, CSDE1, SBDS, HSPA4, IL3, RPL41, AHSA1, LEFTY1, KLF1, FLI1, GABARAPL2, GABARAPL1, BAMBI, RNF19A, CSF2, GRAP2, POLDIP2, MAPK14, CRK, MTUS1, COL3A1, CDA, DBA2, CD38, PRMT3, DDX21, LONP1, FPR2, TRIM27, MAPK8, MAPK1, PIM1, SERPINE1, RPS21, LRPAP1, LEP, IL9, IL1B, TFRC, TNF, CNBP, AIMP2, XRS, HBB, RMRP, TEC

Drugs

Allogeneic multi-virus specific T lymphocytes targeting BK virus, cytomegalovirus, human herpesvirus-6, Epstein Barr virus and adenovirus, haematopoietic stem cells and blood progenitors umbilical cord-derived expanded with (1R, 4R)-N1-(2-benzyl-7-(2-methyl-2H-tetrazol-5-yl)-9H-pyrimido[4,5-b]indol-4-yl)cyclohexane-1,4-diamine dihydrobromide dihydrate

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A number sign (#) is used with this entry because Diamond-Blackfan anemia-9 (DBA9) is caused by heterozygous mutations in the gene encoding ribosomal protein S10 (RPS10; 603632) on chromosome 6p.

Description

Diamond-Blackfan anemia (DBA) is an inherited red blood cell aplasia that usually presents in the first year of life. The main features are normochromic macrocytic anemia, reticulocytopenia, and nearly absent erythroid progenitors in the bone marrow. Patients show growth retardation, and approximately 30 to 50% have craniofacial, upper limb, heart, and urinary system congenital malformations. The majority of patients have increased mean corpuscular volume, elevated erythrocyte adenosine deaminase activity, and persistence of hemoglobin F. However, some DBA patients do not exhibit these findings, and even in the same family, symptoms can vary between affected family members (summary by Landowski et al., 2013).

For a discussion of genetic heterogeneity of Diamond-Blackfan anemia, see DBA1 (105650).

Clinical Features

Gerrard et al. (2013) reported a 4-year-old girl who was diagnosed with Diamond-Blackfan anemia at age 17 months. She was noted to have growth retardation, vitamin D deficiency, and Cathie facies. Her condition was responsive to treatment with steroids.

Molecular Genetics

Doherty et al. (2010) sequenced 35 ribosomal protein genes in a cohort of 117 patients with Diamond-Blackfan anemia who were negative for mutation in 7 known DBA genes and identified 3 mutations in the RPS10 gene in 5 patients (603632.0001-603632.0003). None of the mutations were found in at least 520 chromosomes from a control population of similar, largely European origin. Regarding 4 patients for whom information was available, 3 had been initially responsive to steroids, and 2 were still being treated with steroids, whereas 2 were red blood cell-transfusion dependent. Doherty et al. (2010) estimated that RPS10 mutations are present in about 2.6% of the overall DBA population.

In a 4-year-old girl with DBA, Gerrard et al. (2013) identified a nonsense mutation in the RPS10 gene (R113X; 603632.0003). The mutation was not detected in her parents, suggesting that it occurred de novo.