Increased Prevalence of Congenital Heart Disease in Children With Diamond Blackfan Anemia Suggests Unrecognized Diamond Blackfan Anemia as a Cause of Congenital Heart Disease in the General Population: A Report of the Diamond Blackfan Anemia Registry

Adrianna Vlachos, Diana S Osorio, Evangelia Atsidaftos, Jessica Kang, Mohammad Lutfi Lababidi, Howard S Seiden, Dorota Gruber, Bertil E Glader, Kenan Onel, Jason E Farrar, David M Bodine, Anna Aspesi, Irma Dianzani, Ugo Ramenghi, Steven R Ellis, Jeffrey M Lipton, Adrianna Vlachos, Diana S Osorio, Evangelia Atsidaftos, Jessica Kang, Mohammad Lutfi Lababidi, Howard S Seiden, Dorota Gruber, Bertil E Glader, Kenan Onel, Jason E Farrar, David M Bodine, Anna Aspesi, Irma Dianzani, Ugo Ramenghi, Steven R Ellis, Jeffrey M Lipton

No abstract available

Keywords: anemia, Diamond Blackfan; child; human genetics; humans; mutation.

Figures

Figure. Congenital heart disease in Diamond Blackfan anemia (DBA)

(A) The CHD anomalies in the DBAR included: ventricular septal defect (VSD; 44%), atrial septal defect (ASD; 32.5%), coarctation of the aorta (CoA; 4.4%), pulmonic valve stenosis (PS; 5.3%), Tetralogy of Fallot (TOF; 3.5%), aortic valve stenosis (AS; 2.6%), total anomalous pulmonary venous return (TAPVR; 0.9%) and others (7%). Patent ductus arteriosus and patent foramen ovale were not included. The defects were similar in relative frequency to those found in the general CHD population6, with VSD, ASD, CoA, PS, and TOF being the five most common CHD diagnoses in the DBAR but with the exception that there were no cases of tricuspid atresia (TVA), pulmonary atresia (PVA), hypoplastic left heart syndrome (HLHS), dextro-transposition of the great arteries (D-TGA), truncus arteriosus (TA) or atrioventricular canal (AVC). Due to the limited size, it is difficult to ascertain if any of the diagnoses not found are truly underrepresented in the DBAR. However restricting the analysis to age ≥ 6 months likely precludes representative enrollment of patients with severe fatal lesions. The absence of AVC defects in the DBAR cohort can be explained by the fact that most AVC defects in the general population are usually seen in relation to syndromes, in particular Down syndrome. (B) Northern blot analysis of pre-rRNA processing was performed on total RNA isolated from primary peripheral blood mononuclear cells (left panel) on the DBAR patient and immortalized lymphoblastoid cells lines (right panel) from the Italian patient, and healthy controls, respectively. Protein translations of mutational genotypes for index patients are shown above appropriate lanes. The membranes were interrogated with a probe against the 5′ end of ITS1 represented as the asterisk above the schematic views of pre-rRNA species shown to the right. The values shown below each lane represent the ratio of phosphorimage units derived for 30S and 18SE species in each lane demonstrate increased 30S pre-rRNA and diminished 18SE, consistent with a pre-rRNA processing defect reported in patients with RPS24 mutations.