A De Novo Splicing Mutation of SRP72 in Bone Marrow Failure Syndrome Type 1: Case Report and Review of the Literature.

backgroundSRP72-associated hereditary bone marrow failure syndrome type 1 (BMFS1) has recently been described and only six families have been reported so far. BMFS1 is an autosomal dominant condition characterized by early-onset aplastic anemia or pancytopenia in some patients and adult-onset myelodysplasia in others. This paper presents the clinical and genetic characteristics of a rare case of hereditary bone marrow failure syndrome 1 (BMFS1) and explores its pathogenesis.

methodsBlood samples and clinical data were collected from the proband and his biological parents. Next-generation sequencing (NGS) was employed to sequence the genes associated with the proband, and the identified variants were subsequently confirmed via Sanger sequencing. Additionally, minigene splicing assays were conducted to assess the functional alterations of SRP72.

resultsA new splicing variant, c.1502+1G>A, was identified in the SRP72 gene through gene sequencing, and this finding was confirmed by Sanger sequencing. Neither parent carried this mutation. Minigene splicing assays revealed an insertion of two bases (AG) at the mRNA level (r.1503-2_1503-1insAG), potentially resulting in a premature stop codon (p.Leu502ValfsTer14). According to ACMG guidelines, the variant is classified as "Likely pathogenic". The c.1502+1G>A mutation in SRP72 is implicated as the potential cause of BMFS1 in this child.

conclusionsOur study identified a novel classical splicing mutation, marking the first report of BMFS1 in China. This case broadens the spectrum of pathogenic variants associated with the SRP72 gene and expands our understanding of its phenotypic manifestations. It also serves as a typical example for early diagnosis and appropriate treatment of BMFS1.