1. Genotype-phenotype association and variant characterization in Diamond-Blackfan anemia caused by pathogenic variants in RPL35A
- Author
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D. Matthew Gianferante, Marcin W. Wlodarski, Evangelia Atsidaftos, Lydie Da Costa, Polyxeni Delaporta, Jason E. Farrar, Frederick D. Goldman, Maryam Hussain, Antonis Kattamis, Thierry Leblanc, Jeffrey M. Lipton, Charlotte M. Niemeyer, Dagmar Pospisilova, Paola Quarello, Ugo Ramenghi, Vijay G. Sankaran, Adrianna Vlachos, Jana Volejnikova, Blanche P. Alter, Sharon A. Savage, and Neelam Giri
- Subjects
Diseases of the blood and blood-forming organs ,RC633-647.5 - Abstract
Diamond Blackfan anemia (DBA) is predominantly an autosomal dominant inherited red cell aplasia primarily caused by pathogenic germline variants in ribosomal protein genes. DBA due to pathogenic RPL35A variants has been associated with large 3q29 deletions and phenotypes not common in DBA. We conducted a multi-institutional genotype-phenotype study of 45 patients with DBA associated with pathogenic RPL35A germline variants and curated the variant data on 21 additional cases from the literature. Genotype-phenotype analyses were conducted comparing patients with large deletions versus all other pathogenic variants in RPL35A. Twenty-two of the 45 cases had large deletions in RPL35A. After adjusting for multiple tests, a statistically significant association was observed between patients with a large deletion and steroid-resistant anemia, neutropenia, craniofacial abnormalities, chronic gastrointestinal problems, and intellectual disabilities (p
- Published
- 2020
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