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Clinical and functional characterisation of the SMAD4 germline variant c.1035C > A in a family with juvenile polyposis syndrome by whole-exome sequencing

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Abstract

Juvenile polyposis syndrome (JPS) is a rare autosomal dominant inherited disease characterised by multiple juvenile polyps. Genes with JPS-associated mutations and their correlation with the phenotype are currently unknown. Gastrointestinal endoscopy results of a 31-year-old female patient showed multiple polyps in the digestive tract, and the presence of juvenile polyps was confirmed by pathological examination. During follow-up, the patient underwent total gastrectomy and polypectomy several times. Five members of this family were diagnosed with JPS, of which two died and three survived. Full exon gene sequencing of eight members of this family revealed a SMAD4 (NM-005359.3) c.1035C > A (p.Cys345*) mutation. This mutation leads to premature codon termination, causing protein truncation. SMAD4 is a pathogenic gene associated with JPS. This is the first report of an association between the c.1035C > A mutation and JPS pathogenesis. Detection of JPS-related mutations in family members with a genetic predisposition for JPS is very important for genetic counselling, surgical intervention, long-term monitoring and follow-up, and drug treatment.

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All data generated or analysed during this study are included in this published article.

Abbreviations

JPS:

Juvenile polyposis syndrome

SMAD4:

SMAD family member 4

ACMG:

American College of Medical Genetics

BMPR1A:

Bone morphogenetic protein receptor 1A

PTEN:

Phosphatase and tensin homology deleted on chromosome ten

ENG:

Endoglin

CRC:

Colorectal cancer

TGF-β:

Transforming growth factor-beta

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Acknowledgements

We acknowledge and appreciate the families for their continued support and participation in our studies.

Funding

This research was supported by Youth Cultivation Program of PLA Medical Science and Technology Project (21QNPY138); Natural Science Foundation of Fujian Province (2020J011139).

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Author notes

  1. Yuan Dang and Qianhui Xu auhors have Contributed equally.

Authors and Affiliations

  1. Department of General Surgery, Fuzong Clinical Medical College, Fujian Medical University, Fuzhou, 350025, Fujian, China

    Yuan Dang, Qianhui Xu, Xiaofang Liu, Lie Wang & Chen Lin

  2. Innovation Center for Cancer Research, Fujian Medical University Cancer Hospital, Fujian Cancer Hospital, Fuzhou, Fujian, China

    Yuan Dang

  3. Fujian Key Laboratory of Advanced Technology for Cancer Screening and Early Diagnosis, Fujian Cancer Hospital, Fuzhou, China

    Yuan Dang

  4. Department of General Surgery, 900th hospital of Joint Logistics Support Force, 156 Xierhuan Road, Fuzhou, 350025, Fujian, China

    Qianhui Xu, Xiaofang Liu, Lie Wang & Chen Lin

  5. Department of General Surgery, Dongfang Hospital of Xiamen university, School of Medicine, Xiamen University, 156 Xierhuan Road, Fuzhou, 350025, Fujian, China

    Qianhui Xu, Xiaofang Liu, Lie Wang & Chen Lin

Authors
  1. Yuan Dang
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  2. Qianhui Xu
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  3. Xiaofang Liu
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  4. Lie Wang
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Contributions

YD analysed data. QX and XL participated in samples collected. LW contributed to the major funding support. CL designed the study. QX and YD wrote the manuscript. All authors read and approved the final manuscript.

Corresponding authors

Correspondence to Lie Wang or Chen Lin.

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Conflict of interest

The authors declare that they have no competing interests.

Ethics approval and consent to participate

The present study was approved by the 900th Hospital Ethics Committee (2021–002). All patients provided permission for the use of their serum samples for research purposes.

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Dang, Y., Xu, Q., Liu, X. et al. Clinical and functional characterisation of the SMAD4 germline variant c.1035C > A in a family with juvenile polyposis syndrome by whole-exome sequencing. Med Mol Morphol 56, 78–83 (2023). https://doi.org/10.1007/s00795-022-00333-w

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  • DOI: https://doi.org/10.1007/s00795-022-00333-w

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