Diamond Blackfan anemia (DBA) is an autosomal dominant disorder with a heterogeneous clinical presentation which may include macrocytic anemia typically presenting in the first year of life, growth retardation, and congenital malformations in 30%-50% of patients. This phenotypic variability is partially explained by genotype-phenotype correlations, with several ribosomal protein genes implicated in this disorder. Most cases are due to de novo variants, but familial occurrences highlight variable expressivity and reduced penetrance. To date, one case has been previously reported with a pathogenic variant in the RPL26 gene: a 3.5-year-old female with multiple congenital anomalies and typical hematological features of DBA. Here, we report a novel frameshift variant in RPL26 identified in a proband and his brother with limb malformations without anemia. Decreased RPL26 protein levels were detected in the proband's lymphoblasts. Subsequent clinical workup revealed high erythrocyte adenosine deaminase activity (eADA) in the proband, without anemia. This family represents the second report of RPL26-associated congenital anomalies in the DBA spectrum and further illustrates the non-hematological presentation of Diamond Blackfan "anemia".
Keywords: Diamond Blackfan anemia; RPL26; congenital malformations; erythrocyte ADA; limb anomalies.
© 2024 The Author(s). American Journal of Medical Genetics Part A published by Wiley Periodicals LLC.