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

Xu,Ming; He,Hongsheng; Yang,Zengqiang; Luo,Peng; Wang,Qing; Gao,Feng

doi:10.3892/br.2019.1268

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

Authors:
- Ming Xu
- Hongsheng He
- Zengqiang Yang
- Peng Luo
- Qing Wang
- Feng Gao
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Affiliations: Department of Colorectal and Anal Surgery, The 940th Hospital of Joint Logistics Support Force of The Chinese People's Liberation Army, Lanzhou, Gansu 730050, P.R. China, Shanghai Topgen Bio‑Pharm Co., Ltd., Shanghai 201321, P.R. China, Joint Laboratory of Constitutional Genetics on Frequent Cancers HCL‑CLB, Cancer Genomics Platform, Centre Léon Bérard, Lyon 69008, France
Published online on: December 20, 2019 https://doi.org/10.3892/br.2019.1268
Pages: 134-138

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Abstract

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.

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