MutL homolog 1 germline mutation c.(453+1_454-1)_(545+1_546-1)del identified in lynch syndrome: A case report and review of literature

Abstract

Background: Lynch syndrome (LS) is an autosomal dominant hereditary disorder because of germline mutations in DNA mismatch repair genes, such as MutL homolog 1 (MLH1), PMS1 homolog 2, MutS homolog 2, and MutS homolog 6. Gene mutations could make individuals and their families more susceptible to experiencing various malignant tumors. In Chinese, MLH1 germline mutation c.(453+1_454-1)_(545+1_546-1)del-related LS has been infrequently reported. Therefore, we report a rare LS patient with colorectal and endometrioid adenocarcinoma and describe her pedigree characteristics.

Case summary: A 57-year-old female patient complained of irregular postmenopausal vaginal bleeding for 6 mo. She was diagnosed with LS, colonic malignancy, endometrioid adenocarcinoma, secondary fallopian tube malignancy, and intermyometrial leiomyomas. Then, she was treated by abdominal hysterectomy, bilateral oviduct oophorectomy, and sentinel lymph node resection. Genetic testing was performed using next-generation sequencing technology to detect the causative genetic mutations. Moreover, all her family members were offered a free genetic test, but no one accepted it.

Conclusion: No tumor relapse or metastasis was found in the patient during the 30-mo follow-up period. The genetic panel sequencing showed a novel pathogenic germline mutation in MLH1, c.(453+1_454-1)_(545+1_546-1)del, for LS. Moreover, cancer genetic counseling and testing are still in the initial development state in China, and maybe face numerous challenges in the further.

Keywords: Case report; Colorectal cancer; Endometrial cancer; Gene testing; Lynch syndrome; MLH1 gene.

Figure 1

Preoperative abdominal magnetic resonance imaging. A: Sagittal magnetic resonance imaging (MRI) showed an equal T1 and slightly longer T2 signal in the uterine cavity; B: Coronal MRI image; C: Axial MRI image. D: Enhanced MRI image showing that the lesions were inhomogeneous enhanced. The white arrowheads represent lesions. The tumor size was approximately 31 mm × 23 mm (B and C).

Figure 2

Immunohistochemical images. A: Loss of MLH1 proteins was found in the tumor cells; B: Expression of MSH2 protein was detected in the tumor cells; C: Expression of MSH6 protein was detected in the tumor cells; D: Loss of PMS2 protein was found in the tumor cells.

Figure 3

Figures related to gene test results. A deletion mutation of exon 6 was found in the MLH1 gene.

Figure 4

Family pedigree. The reconstructed pedigree demonstrates that the proband (II-9), her mother (I-1), her sisters (II-1, II-3, and II-5) and her brother (II-7), and her sister’s son (IV-4) experienced cancer. I-1 was diagnosed with colon cancer at 55 years and died at 70 years. II-1 and II-3, both at 60 years, suffered from colon cancer and endometrial cancer, respectively. II-5 experienced colon cancer at 40 years and endometrial cancer at 48 years. II-7 developed polyps of the colon at unknown age. III-4 had colon cancer at 25 years and died at 27 years. The arrow indicates the proband. Solid symbols reveal persons affected by malignancy. The symbol with a slash indicates a deceased individual with age at death. Circles indicate female family members, and squares suggest male family members.