Diagnosis and treatment of Diamond-Blackfan anemia and Pierre-Robin sequence caused by a novel mutation of RPS28 gene.

Background: Diamond-Blackfan anemia (DBA) is a congenital erythroid aplasia associated with physical anomalies and a predisposition to cancer. It is categorized as ribosomopathy related to heterozygous allelic variations in ribosomal protein (RP) genes. Pierre Robin sequence (PRS) is a rare and etiologically heterogeneous condition, defined by the clinical triad of micrognathia, glossoptosis, and cleft palate.

Methods and results: We present a 5-year-and-2-month-old Chinese boy diagnosed with DBA combined with RPS. He was born with micrognathia, cleft palate, and airway obstruction, resulting in neonatal asphyxia and feeding difficulties, which constitute the classic triad of PRS. Low-set ears, downslanted palpebral fissures, bilateral exotropia, a short neck, hypertelorism, a thenar muscle defect, and bilateral severe sensorineural hearing loss were also observed in the boy. His motor and speech development were significantly delayed. In addition, he was found to be granulocytopenic at birth and severely anemic at 2 years and 10 months of age. Whole exome sequencing of peripheral blood revealed a heterozygous mutation in the RPS28 gene (c.2T > C, p.Met1?), a novel pathogenic mutation in RPS28. RPS28 is one of the ribosomal protein (RP) genes, which may contribute to DBA-related phenotypes. The boy underwent HSCT from 9/10 HLA-matched donor and his neutrophil and hemoglobin levels returned to normal.

Conclusion: It is crucial to perform a genetic evaluation for syndromic bone marrow failure with congenital anomalies. A heterozygous mutation in the RPS28 gene (c.2T > C, p.Met1?) is a novel pathogenic mutation associated with DBA. HSCT is an effective treatment for hematological abnormalities in DBA.