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

## TL;DR

A 6-year-old child with bone marrow failure was found to have a new mutation in the SRP72 gene, offering insights into the genetic basis of this rare condition.

## Contribution

This is the first reported case of BMFS1 in China and identifies a novel de novo splicing mutation in SRP72.

## Key findings

- A de novo splicing mutation (c.1502+1G>A) in SRP72 was identified in a child with BMFS1.
- The mutation leads to abnormal mRNA splicing and a frameshift mutation (p.Leu502ValfsTer14).
- This case expands the known mutation spectrum of SRP72 and highlights the importance of genetic testing for BMFS1.

## Abstract

SRP72‐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.

Blood 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.

A 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.

Our 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.

This study reports a rare case of bone marrow failure syndrome type 1 (BMFS1) caused by a novel de novo splicing mutation (c.1502+1G>A) in the SRP72 gene. The 6‐year‐old patient presented with aplastic anemia and pancytopenia. Genetic analysis identified the mutation, which was absent in both parents, confirming its de novo origin. Mini‐gene assays demonstrated that the mutation leads to abnormal mRNA splicing, resulting in a frameshift mutation and premature stop codon (p.Leu502ValfsTer14). This is the first reported case of BMFS1 in China, expanding the mutation spectrum of SRP72 and highlighting the importance of genetic testing in diagnosing BMFS1. The findings provide new insights into the molecular mechanisms of BMFS1 and underscore the role of SRP72 in bone marrow failure.