Diagnosis of a case of homozygous constitutional MMR-deficiency by the use of a gene-panel in a non-consanguineous family: A case report.

Constitutional MMR-deficiency syndrome (CMMRD) is a rare but severe hereditary syndrome of pediatric cancer caused by bi-allelic pathogenic variants in one of the mismatch DNA repair genes (MMR): MLH1, MSH2, MSH6, and PMS2. This syndrome occurs when patients inherit altered alleles from both of their heterozygote parents affected by Lynch syndrome. In total, ~150 patients have been identified at present, the majority of which were Caucasian. The present case report described the diagnosis of CMMRD in a Chinese boy with atypical clinical features caused by a homozygous pathogenic variant in MSH6 gene, identified by the use of a gene-panel. This is the first case diagnosed in a Chinese (Asian) population. These data indicated that CMMRD affects patients of any ethnic origin, implying a potentially high prevalence. Notably, the homozygous bi-allelic inactivation was caused by a random event in an apparently closed population, as opposed to a consanguineous marriage, additionally suggesting a high risk of CMMRD for individuals living in relatively closed populations.