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

• Published in: Familial cancer 2024-11, Vol.23 (4), p.515-522
• Main Authors: Abdelmaksoud-Dammak, Rania, Ammous-Boukhris, Nihel, BenAyed-Guerfali, Dorra, Gdoura, Yassine, Boujelben, Imen, Guidara, Souhir, Charfi, Slim, Boudabbous, Wiem, Ammar, Saloua, Rhaiem, Wiem, Boudawara, Mohamed Zaher, Kamoun, Hassen, Sallemi-Boudawara, Tahya, Mhiri, Riadh, Mokdad-Gargouri, Raja
• Format: Article
• Language: English
• Subjects: Astrocytoma; Astrocytoma - diagnosis; Astrocytoma - genetics; Astrocytoma - therapy; Biomedical and Life Sciences; Biomedicine; Brain Neoplasms - diagnosis; Brain Neoplasms - genetics; Brain Neoplasms - therapy; Cancer Research; Child; Children; Colorectal carcinoma; Colorectal Neoplasms - diagnosis; Colorectal Neoplasms - genetics; Colorectal Neoplasms - therapy; Developing Countries; Diagnosis; DNA-Binding Proteins - genetics; Epidemiology; Exome Sequencing; Female; Germ-Line Mutation; Human Genetics; Humans; Immunohistochemistry; Male; Mismatch repair; MSH2 protein; MSH6 gene; MSH6 protein; MutS Homolog 2 Protein - genetics; Neoplastic Syndromes, Hereditary - diagnosis; Neoplastic Syndromes, Hereditary - genetics; Neoplastic Syndromes, Hereditary - therapy; Original Article; Pedigree; Tunisia; Whole genome sequencing; Yeast
• ISSN: 1389-9600; 1573-7292; 1573-7292
• DOI: 10.1007/s10689-024-00386-z

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.