| *[[Diamond-Blackfan anemia]] is characterized by a block in erythropoiesis which is due to the ribosomal protein gene mutation in about 80-85% of those affected. <ref name="pmid30503522">{{cite journal |vauthors=Ulirsch JC, Verboon JM, Kazerounian S, Guo MH, Yuan D, Ludwig LS, Handsaker RE, Abdulhay NJ, Fiorini C, Genovese G, Lim ET, Cheng A, Cummings BB, Chao KR, Beggs AH, Genetti CA, Sieff CA, Newburger PE, Niewiadomska E, Matysiak M, Vlachos A, Lipton JM, Atsidaftos E, Glader B, Narla A, Gleizes PE, O'Donohue MF, Montel-Lehry N, Amor DJ, McCarroll SA, O'Donnell-Luria AH, Gupta N, Gabriel SB, MacArthur DG, Lander ES, Lek M, Da Costa L, Nathan DG, Korostelev AA, Do R, Sankaran VG, Gazda HT |title=The Genetic Landscape of Diamond-Blackfan Anemia |journal=Am. J. Hum. Genet. |volume=103 |issue=6 |pages=930–947 |date=December 2018 |pmid=30503522 |pmc=6288280 |doi=10.1016/j.ajhg.2018.10.027 |url=}}</ref>
| |
| *Sporadic mutation(55%) occurs in genes encoding several different ribosomal proteins, although based on the latest studies, approximately 40 – 45% of DBA cases are hereditary which are inherited with an autosomal dominant inheritance, means that a single copy of an altered gene in each cell is adequate to cause the disorder and is inherited from one affected parent.<ref name="pmid22160079">{{cite journal |vauthors=Ball S |title=Diamond Blackfan anemia |journal=Hematology Am Soc Hematol Educ Program |volume=2011 |issue= |pages=487–91 |date=2011 |pmid=22160079 |doi=10.1182/asheducation-2011.1.487 |url=}}</ref><ref name="pmid23744582">{{cite journal |vauthors=Garçon L, Ge J, Manjunath SH, Mills JA, Apicella M, Parikh S, Sullivan LM, Podsakoff GM, Gadue P, French DL, Mason PJ, Bessler M, Weiss MJ |title=Ribosomal and hematopoietic defects in induced pluripotent stem cells derived from Diamond Blackfan anemia patients |journal=Blood |volume=122 |issue=6 |pages=912–21 |date=August 2013 |pmid=23744582 |pmc=3739037 |doi=10.1182/blood-2013-01-478321 |url=}}</ref> and they have a family history of the disease with varying phenotypes.<ref name="pmid30228860">{{cite journal |vauthors=Da Costa L, Narla A, Mohandas N |title=An update on the pathogenesis and diagnosis of Diamond-Blackfan anemia |journal=F1000Res |volume=7 |issue= |pages= |date=2018 |pmid=30228860 |pmc=6117846 |doi=10.12688/f1000research.15542.1 |url=}}</ref> about 25% of patients have mutations in the [[ribosomal|ribosome]] protein S19 (RPS19) gene on chromosome 19 at [[cytogenetic]] position 19q13.2. RPS19 protein has been demonstrated to play an important role in 18S rRNA maturation in yeast and in human cells. However, the disease characterized by genetic [[heterogeneity]] and other mutated genes also been found in RPL5, RPL11, RPL35A, RPS7, RPS10, RPS17, RPS24, and RPS26, and rarely in RPL15, RPL17, RPL19, RPL26, RPL27, RPL31, RPS15A, RPS20, RPS27, RPS28, RPS29, that result in alterations of pre-RNA processing and small or large ribosomal subunit synthesis which were demonstrated in human cells with RPL11, RPL35A, RPS24, and RPL26, RPS7 deficiency<ref name="pmid18230666">{{cite journal |vauthors=Choesmel V, Fribourg S, Aguissa-Touré AH, Pinaud N, Legrand P, Gazda HT, Gleizes PE |title=Mutation of ribosomal protein RPS24 in Diamond-Blackfan anemia results in a ribosome biogenesis disorder |journal=Hum. Mol. Genet. |volume=17 |issue=9 |pages=1253–63 |date=May 2008 |pmid=18230666 |doi=10.1093/hmg/ddn015 |url=}}</ref> , also "non-RP" genes such as TSR2 and GATA1. TSR2 plays a role in ribosome biogenesis since it is involved in the pre-rRNA processing and binds to RPS26.GATA1 which is the major erythroid transcription factor as being essential for precursor cells to differentiate into red blood cells and plays a critical role in regulating normal erythroid differentiation by activating an array of erythroid genes. Researchers found DBA mutations reduce the actual numbers of ribosomes in blood precursor cells. Without enough ribosomes, the precursors can’t produce enough GATA1, so mature red cells never form. Other blood cells — like platelets, T cells, and B cells — can still develop since they’re not dependent on GATA1.<ref name="pmid28377399">{{cite journal |vauthors=O'Brien KA, Farrar JE, Vlachos A, Anderson SM, Tsujiura CA, Lichtenberg J, Blanc L, Atsidaftos E, Elkahloun A, An X, Ellis SR, Lipton JM, Bodine DM |title=Molecular convergence in ex vivo models of Diamond-Blackfan anemia |journal=Blood |volume=129 |issue=23 |pages=3111–3120 |date=June 2017 |pmid=28377399 |pmc=5465839 |doi=10.1182/blood-2017-01-760462 |url=}}</ref><ref name="pmid28615220">{{cite journal |vauthors=Ulirsch JC, Lareau C, Ludwig LS, Mohandas N, Nathan DG, Sankaran VG |title=Confounding in ex vivo models of Diamond-Blackfan anemia |journal=Blood |volume=130 |issue=9 |pages=1165–1168 |date=August 2017 |pmid=28615220 |pmc=5580274 |doi=10.1182/blood-2017-05-783191 |url=}}</ref><ref name="pmid24999938">{{cite journal |vauthors=Boultwood J, Pellagatti A |title=Reduced translation of GATA1 in Diamond-Blackfan anemia |journal=Nat. Med. |volume=20 |issue=7 |pages=703–4 |date=July 2014 |pmid=24999938 |doi=10.1038/nm.3630 |url=}}</ref><ref name="pmid24952648">{{cite journal |vauthors=Ludwig LS, Gazda HT, Eng JC, Eichhorn SW, Thiru P, Ghazvinian R, George TI, Gotlib JR, Beggs AH, Sieff CA, Lodish HF, Lander ES, Sankaran VG |title=Altered translation of GATA1 in Diamond-Blackfan anemia |journal=Nat. Med. |volume=20 |issue=7 |pages=748–53 |date=July 2014 |pmid=24952648 |pmc=4087046 |doi=10.1038/nm.3557 |url=}}</ref><ref name="pmid29551269">{{cite journal |vauthors=Khajuria RK, Munschauer M, Ulirsch JC, Fiorini C, Ludwig LS, McFarland SK, Abdulhay NJ, Specht H, Keshishian H, Mani DR, Jovanovic M, Ellis SR, Fulco CP, Engreitz JM, Schütz S, Lian J, Gripp KW, Weinberg OK, Pinkus GS, Gehrke L, Regev A, Lander ES, Gazda HT, Lee WY, Panse VG, Carr SA, Sankaran VG |title=Ribosome Levels Selectively Regulate Translation and Lineage Commitment in Human Hematopoiesis |journal=Cell |volume=173 |issue=1 |pages=90–103.e19 |date=March 2018 |pmid=29551269 |pmc=5866246 |doi=10.1016/j.cell.2018.02.036 |url=}}</ref> In the remaining 10-15% of DBA cases, no abnormal genes have yet been identified. It is likely that mutations are in a regulatory region including intronic regions and promoters in one of the known RP genes may account for the DBA phenotype. <ref name="pmid30228860">{{cite journal |vauthors=Da Costa L, Narla A, Mohandas N |title=An update on the pathogenesis and diagnosis of Diamond-Blackfan anemia |journal=F1000Res |volume=7 |issue= |pages= |date=2018 |pmid=30228860 |pmc=6117846 |doi=10.12688/f1000research.15542.1 |url=}}</ref>
| |