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Strategies for diagnosis and management of CMMRD in low-resource countries: report of a Tunisian family

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Abstract

Constitutional Mismatch Repair Deficiency (CMMRD) is a rare childhood cancer predisposition syndrome, caused by biallelic pathogenic germline variants in the mismatch repair genes. Diagnosis and management of this syndrome is challenging, especially in low-resource settings. This study describes a patient diagnosed with colorectal cancer and grade 3 astrocytoma at the age of 11 and 12 respectively. Immunohistochemistry analysis showed a loss of MSH2 and MSH6 protein expression in CRC tissues of the patient. We identified by Targeted Exome Sequencing a homozygous pathogenic germline variant in exon 9 of the MSH6 gene (c.3991 C > T; p.Ala1268Glyfs*6). Genetic investigation of the family showed that the father was heterozygous for the identified pathogenic variant while the brother was wild type for this variant. Our study highlights the importance of a correct and timely diagnosis of CMMRD which can have implications for treatment. It also underlines the imperative need to enhance awareness, diagnostic standards, and surveillance that are crucial for patients and their families.

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The original contributions presented in the study are included in the article. Further inquiries can be directed to the corresponding author.

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Acknowledgements

This research was supported by the grant of Tunisian ministry of higher education and scientific research. We thank the members of the family for their cooperation and the technical support of N. Kchaou from CBS for Miseq and SeqStudio manipulation.

Funding

This research was supported by the grant of Tunisian ministry of higher education and scientific research (Grant: LR19CBS02).

Author information

Authors and Affiliations

  1. Department of Cancer Genetics, Laboratory of Molecular Biotechnology of Eukaryotes, Center of Biotechnology of Sfax, University of Sfax BPK 1177, Sfax, 3018, Tunisia

    Rania Abdelmaksoud-Dammak, Nihel Ammous-Boukhris, Dorra BenAyed-Guerfali & Raja Mokdad-Gargouri

  2. Department of Neurosurgery, Habib Bourguiba Hospital, University of Sfax, Sfax, Tunisia

    Yassine Gdoura, Wiem Boudabbous & Mohamed Zaher Boudawara

  3. Department of Human Genetics, Hedi Chaker Hospital, University of Sfax, Sfax, Tunisia

    Imen Boujelben, Souhir Guidara & Hassen Kamoun

  4. Department of Anatomopathology, Habib Bourguiba Hospital, University of Sfax, Sfax, Tunisia

    Slim Charfi & Tahya Sallemi-Boudawara

  5. Department of Pediatric Surgery, Hedi Chaker Hospital, University of Sfax, Sfax, Tunisia

    Saloua Ammar, Wiem Rhaiem & Riadh Mhiri

Authors
  1. Rania Abdelmaksoud-Dammak
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  2. Nihel Ammous-Boukhris
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Contributions

R.AD, N.AB and D.BG performed NGS experiment, data analysis and interpretation. R.AD and N.AB performed MSI testing. Y.G, I.B, S.G conceived the study. S.C and T.SB performed and interpreted immunohistochemistry data. R.AD and R.MG conceived and wrote the manuscript. I.B, S.G and H.K contributed to genetic counseling. Y.G, W.B, M.ZB, S.A, W.R and R.M participated in the patient’s clinical care and contributed to writing manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Raja Mokdad-Gargouri.

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Ethical approval

This study was approved by Ethics Committee of CHU Habib Bourguiba/Hedi Chaker Hospitals.

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Written informed consent was obtained from the patient father to publish this study in accordance with the journal’s patient consent policy.

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The authors declare they have no financial or commercial interests that could be considered as a potential conflict of interest.

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Abdelmaksoud-Dammak, R., Ammous-Boukhris, N., BenAyed-Guerfali, D. et al. Strategies for diagnosis and management of CMMRD in low-resource countries: report of a Tunisian family. Familial Cancer (2024). https://doi.org/10.1007/s10689-024-00386-z

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