Diamond-Blackfan Anemia 5

A number sign (#) is used with this entry because Diamond-Blackfan anemia-5 (DBA5) is caused by heterozygous mutation in the gene encoding ribosomal protein L35A (RPL35A; 180468) on chromosome 3q29.

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).

Using a candidate gene strategy combining high-resolution genomic mapping and gene expression microarray, Farrar et al. (2008) analyzed the chromosome 3q29-qter and 3q29 deletions, respectively, from a 9-year-old boy and an unrelated 7-week-old girl with Diamond-Blackfan anemia, and identified RPL35A (180468) as a potential DBA gene. The authors then screened genomic DNA from 148 additional probands with DBA, including 11 probands with known mutations in RPS19 (603474) and 3 with known mutations in RPS24 (602412); heterozygous mutations were identified in the RPL35A gene in 1 familial (180468.0001) and 2 sporadic cases (180468.0002 and 180468.0003), for an estimated 3.3% rate of RPL35A abnormalities in DBA probands. In the familial case, the mutation was also found in the proband's father and sister, who had untreated macrocytic anemia suggestive of subclinical DBA. None of the mutations were found in 180 normal controls.