PMC10448983_01
Clinical and molecular analysis of the LS family. (A) Pedigree structure of the LS family. The arrow indicates the proband (III-4). (B) Enhanced CT and electronic colonoscopy images of the proband (III-4). (C) Image of tumor specimen after subtotal colectomy of the proband (III-4). Arrows indicate adenocarcinoma and adenoma. (D) H&E staining of tumor and polyp tissues. (E) IHC staining for MMR proteins in the tumor and polyp tissues. (F) Landscape of gene mutations. (G) MLH1 c.482delC was shown by using the Integrative Genomics Viewer (IGV). (H) 3D structure modeling of mutant MLH1 protein. (I) Sequencing chromatograms of MLH1 exon 6 regions in affected members. Scale bars: 100 and 50 mum.
goad049f1.jpg
PMC10448983_02_goad049f1.jpg
goad049-F1
The IHC staining of the colon tumor and adenoma polyps showed the loss of MLH1 and PMS2 expression (Figure 1E); the MSI testing report (2B3D NCI Panel) also demonstrated MSI-high in tumor tissues. Society nomenclature, next-generation sequencing analysis identified a novel variant, NM_000249.4(MLH1):c.482delC (p.Thr161ArgfsTer6) heterozygous (Figure 1F and G), and the variant was pathogenic when using in silico analysis. Swiss-Model revealed that the mutant amino acid changed the protein transcription and translation, resulting in the loss of the MLH1 mismatch repair function (Figure 1H). Two family members (II-5 and II-7) were also identified to carry this pathogenic variant (Figure 1I).
PMC10448983_02
Clinical and molecular analysis of the LS family. (A) Pedigree structure of the LS family. The arrow indicates the proband (III-4). (B) Enhanced CT and electronic colonoscopy images of the proband (III-4). (C) Image of tumor specimen after subtotal colectomy of the proband (III-4). Arrows indicate adenocarcinoma and adenoma. (D) H&E staining of tumor and polyp tissues. (E) IHC staining for MMR proteins in the tumor and polyp tissues. (F) Landscape of gene mutations. (G) MLH1 c.482delC was shown by using the Integrative Genomics Viewer (IGV). (H) 3D structure modeling of mutant MLH1 protein. (I) Sequencing chromatograms of MLH1 exon 6 regions in affected members. Scale bars: 100 and 50 mum.
goad049f1.jpg
PMC10448983_02_goad049f1.jpg
goad049-F1
The IHC staining of the colon tumor and adenoma polyps showed the loss of MLH1 and PMS2 expression (Figure 1E); the MSI testing report (2B3D NCI Panel) also demonstrated MSI-high in tumor tissues. Society nomenclature, next-generation sequencing analysis identified a novel variant, NM_000249.4(MLH1):c.482delC (p.Thr161ArgfsTer6) heterozygous (Figure 1F and G), and the variant was pathogenic when using in silico analysis. Swiss-Model revealed that the mutant amino acid changed the protein transcription and translation, resulting in the loss of the MLH1 mismatch repair function (Figure 1H). Two family members (II-5 and II-7) were also identified to carry this pathogenic variant (Figure 1I).