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

Sep 28, 2026

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SRP72-associated hereditary bone marrow failure syndrome type 1 (BMFS1) is a rare autosomal dominant disorder described in only a few families. This study reports the clinical and genetic features of a rare BMFS1 case, investigating disease mechanism through blood and clinical data collection, next-generation sequencing with variant confirmation by Sanger sequencing, and minigene splicing assays to determine functional RNA changes.

LanguageEnglish

CategoryHealthcare

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Pages8

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Introduction

Materials and Methods

Results

Conclusions

Molecular Genetics & Genomic Medicine |
CLINICAL REPORT OPEN ACCESS
A De Novo Splicing Mutation of SRP72 in Bone Marrow Failure Syndrome Type 1: Case Report and Review of the Literature
Wang Xiangwen1 | Zhang Duo2 | Hao Wenjing3 | Hou Hui4
1Department of Pediatric, Xiaogan First People's Hospital, Xiaogan, China | 2Baotou Medical College, Inner Mongolia University of Science and Technology, Baotou, China | 3Department of Science and Education, Chifeng Hospital, Chifeng, China | 4Department of Pediatric Hematology, Inner
Mongolia Autonomous Region People's Hospital, Hohhot, China Correspondence: Wang Xiangwen ([18047192454@163.com](18047192454@163.com))
Received: 4 August 2024 | Revised: 26 March 2025 | Accepted: 9 December 2025
Keywords: bone marrow failure syndrome type 1 | case report | minigene | SRP72 | | | --- | --- | | ABSTRACT
Background: 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.
Methods: 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 .
Results: 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.
Conclusions: 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 . | | | 1 | Introduction | DiamondBlackfan anemia (DBA), and Shwachman-Diamond syndrome (SDS) (Dokal et al. 2022; Kim et al. 2022) . Their | | Inherited bone marrow failure syndromes (BMFS) com- | hallmark features include single-lineage cytopenia or pancy- | | prise a heterogeneous group of life-threatening diseases, in- | topenia, congenital malformations, bone marrow hematopoi- | | cluding Fanconi anemia (FA), dyskeratosis congenita (DC), | etic failure, and increased susceptibility to tumors (Bluteau | | Abbreviations: AA, aplastic anemia; BMFS1, bone marrow failure syndrome type 1; HSCT, hematopoietic stem cell transplantation; NGS, next generation sequencing; SRP, signal recognition particle.
Wang Xiangwen and Zhang Duo are co-first authors. | | | This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
© 2025 The Author(s). Molecular Genetics & Genomic Medicine published by Wiley Periodicals LLC. | | Molecular Genetics & Genomic Medicine, 2026; 14:e70168 1 of 8 [https://doi.org/10.1002/mgg3.70168](https://doi.org/10.1002/mgg3.70168) et al. 2018; Li and Bledsoe 2023) . BMFS1 (OMIM: \#614675) is a rare form of BMFS caused by mutations in the SRP72 gene (OMIM: \#60

FAQs

What BMFS1 features are associated with SRP72 mutations?

BMFS1 is characterized by early-onset aplastic anemia or pancytopenia in some patients, and adult-onset myelodysplasia in others. The study focuses on SRP72-related hereditary BMFS1.

What genetic variant was identified in this case?

A novel splicing variant, c.1502+1G>A, in the SRP72 gene was identified by sequencing and confirmed by Sanger sequencing. The mutation was not carried by either parent.

How were the functional effects of the splicing variant assessed?

Minigene splicing assays were used to evaluate functional alterations at the mRNA level. The assay suggested insertion of two bases (AG), potentially creating a premature stop codon and supporting a likely pathogenic classification.

Sep 28, 2026

Uploaded by McQueen