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^{1

2}, Diana S Osorio^{3

2

4}, Evangelia Atsidaftos^{3

2}, Jessica Kang^{3

5}, Mohammad Lutfi Lababidi³, Howard S Seiden^{6

7}, Dorota Gruber^{3

6}, Bertil E Glader⁸, Kenan Onel^{3

2

9}, Jason E Farrar¹⁰, David M Bodine⁵, Anna Aspesi¹¹, Irma Dianzani¹¹, Ugo Ramenghi¹², Steven R Ellis^{13

14}, Jeffrey M Lipton^{3

2}

Affiliations

¹ The Feinstein Institute for Medical Research, Northwell Health, Manhasset, NY (A.V., D.S.O., E.A., J.K., M.L.L., D.G., K.O., J.M.L.) avlachos@northwell.edu.
² Division of Hematology/Oncology, and Stem Cell Transplantation (A.V., D.S.O., E.A., K.O., J.M.L.).
³ The Feinstein Institute for Medical Research, Northwell Health, Manhasset, NY (A.V., D.S.O., E.A., J.K., M.L.L., D.G., K.O., J.M.L.).
⁴ Division of Pediatric Hematology/Oncology, Nationwide Children's Hospital, The Ohio State University, Columbus, OH (D.S.O.).
⁵ Genetics and Molecular Biology Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD (J.K., D.M.B.).
⁶ Division of Pediatric Cardiology (H.S.S., D.G.).
⁷ Division of Cardiology, Department of Pediatrics, Icahn School of Medicine at Mount Sinai, New York, NY (H.S.S.).
⁸ Division of Hematology/Oncology, Lucile Packard Children's Hospital Stanford, Palo Alto, CA (B.E.G.).
⁹ Division of Genetics and Genomics (K.O.), Cohen Children's Medical Center, Northwell Health, New Hyde Park, NY.
¹⁰ Department of Pediatrics, Section of Hematology and Oncology, Arkansas Children's Research Institute, University of Arkansas for Medical Sciences, Little Rock, AR (J.E.F.).
¹¹ Department of Health Sciences, University of Piemonte Orientale, Novara, Italy (A.A., I.D.).
¹² Department of Public Health and Pediatric Sciences, University of Torino, Italy (U.R.).
¹³ Department of Biochemistry (S.R.E.).
¹⁴ Department of Molecular Genetics (S.R.E.), University of Louisville, KY.

PMID: 29748317
PMCID: PMC5951415
DOI: 10.1161/CIRCGENETICS.117.002044

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 et al. Circ Genom Precis Med. 2018 May.

. 2018 May;11(5):e002044.

doi: 10.1161/CIRCGENETICS.117.002044.

Authors

Affiliations

¹ The Feinstein Institute for Medical Research, Northwell Health, Manhasset, NY (A.V., D.S.O., E.A., J.K., M.L.L., D.G., K.O., J.M.L.) avlachos@northwell.edu.
² Division of Hematology/Oncology, and Stem Cell Transplantation (A.V., D.S.O., E.A., K.O., J.M.L.).
³ The Feinstein Institute for Medical Research, Northwell Health, Manhasset, NY (A.V., D.S.O., E.A., J.K., M.L.L., D.G., K.O., J.M.L.).
⁴ Division of Pediatric Hematology/Oncology, Nationwide Children's Hospital, The Ohio State University, Columbus, OH (D.S.O.).
⁵ Genetics and Molecular Biology Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD (J.K., D.M.B.).
⁶ Division of Pediatric Cardiology (H.S.S., D.G.).
⁷ Division of Cardiology, Department of Pediatrics, Icahn School of Medicine at Mount Sinai, New York, NY (H.S.S.).
⁸ Division of Hematology/Oncology, Lucile Packard Children's Hospital Stanford, Palo Alto, CA (B.E.G.).
⁹ Division of Genetics and Genomics (K.O.), Cohen Children's Medical Center, Northwell Health, New Hyde Park, NY.
¹⁰ Department of Pediatrics, Section of Hematology and Oncology, Arkansas Children's Research Institute, University of Arkansas for Medical Sciences, Little Rock, AR (J.E.F.).
¹¹ Department of Health Sciences, University of Piemonte Orientale, Novara, Italy (A.A., I.D.).
¹² Department of Public Health and Pediatric Sciences, University of Torino, Italy (U.R.).
¹³ Department of Biochemistry (S.R.E.).
¹⁴ Department of Molecular Genetics (S.R.E.), University of Louisville, KY.

PMID: 29748317
PMCID: PMC5951415
DOI: 10.1161/CIRCGENETICS.117.002044

No abstract available

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

PubMed Disclaimer

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.

See this image and copyright information in PMC

References

1. Vlachos A, Blanc L, Lipton JM. Diamond Blackfan anemia: a model for the translational approach to understanding human disease. Expert Rev Hematol. 2014;7:359–72. - PubMed
1. Lipton JM. Inherited thrombocytopenia and Occam’s razor. Blood. 2017;130:839–840. - PubMed
1. Reller MD, Strickland MJ, Riehle-Colarusso T, Mahle WT, Correa A. Prevalence of congenital heart defects in metropolitan Atlanta, 1998-2005. J Pediatr. 2008;153:807–13. - PMC - PubMed
1. Fargo JH, Kratz CP, Giri N, Savage SA, Wong C, Backer K, et al. Erythrocyte adenosine deaminase: diagnostic value for Diamond-Blackfan anaemia. Br J Haematol. 2013;160:547–54. - PMC - PubMed
1. Fahed AC, Gelb BD, Seidman JG, Seidman CE. Genetics of congenital heart disease: the glass half empty. Circ Res. 2013;112:707–20. - PMC - PubMed

Publication types

Actions
Actions
Actions

MeSH terms

Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions

Grants and funding

LinkOut - more resources

Full Text Sources
Other Literature Sources
- H1 Connect - Access expert opinions and insights on biomedical research.
- scite Smart Citations
Medical
- ClinicalTrials.gov
- MedlinePlus Health Information

Save citation to file

Email citation

Add to Collections

Add to My Bibliography

Your saved search

Create a file for external citation management software

Your RSS Feed

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

Affiliations

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

Authors

Affiliations

Figures

References

Publication types

MeSH terms

Grants and funding

LinkOut - more resources

Full Text Sources

Other Literature Sources

Medical