Whole Exome Sequencing Identifies Two Novel Mutations in a Patient with UC Associated with PSC and SSA.

Dong Wu,Dan Chen,Jiaming Qian,Wen Shi,Wei Liu,Weixun Zhou

doi:10.1155/2021/9936932

Dong Wu, Dan Chen + Show 4 more

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https://doi.org/10.1155/2021/9936932

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Background Patients diagnosed with ulcerative colitis (UC) associated with primary sclerosis cholangitis (PSC) and sessile serrated adenoma (SSA) are rare. The present study aimed to identify the potential causative gene mutation in a patient with UC associated with PSC and SSA. Methods DNA was extracted from the blood sample and tissue sample of SSA, followed by the whole exome sequencing (WES) analysis. Bioinformatics analysis was utilized to predict the deleteriousness of the identified variants. Multiple sequence alignment and conserved protein domain analyses were performed using online software. Sanger sequencing was used to validate the identified variants. Expression and diagnostic analysis of identified mutated genes was performed in the GSE119600 dataset (peripheral blood samples of PSC and UC) and GSE43841 dataset (tumor samples of SSA). Results In the present study, a total of 842 single nucleotide variants (SNVs) in 728 genes were identified in the blood sample. Two variants, integrin beta 4 (ITGB4) (c.C2503G; p.P835A) and a mucin 3A (MUC3A) (c.C1019T; p.P340L), were further analyzed. MUC3A was associated with inflammatory bowel disease. Sanger sequence in blood revealed that the ITGB4 mutation was fully cosegregated with the result of WES in the patient. Additionally, a variant, tumor protein p53 gene (TP53) (c.86delA; p.N29Tfs∗15) was identified in the tissue sample of SSA. Compared to that in normal controls, ITGB4 was upregulated in both UC and PSC, MUC3A was, respectively, upregulated and downregulated in PSC and UC, and TP53 was downregulated in SSA. ITGB4 and TP53 had a potential diagnostic value for UC, PSC and SSA. Conclusions The present study demonstrated that the ITGB4 (c.C2503G; p.P835A) and MUC3A (c.C1019T; p.P340L) mutations may be the potential causative variants in a patient with UC associated with PSC and SSA. TP53 (c.86delA; p.N29Tfs∗15) mutation may be associated with SSA in this patient.

Highlights

Patients diagnosed with ulcerative colitis (UC) associated with primary sclerosis cholangitis (PSC) and sessile serrated adenoma (SSA) are rare. e present study aimed to identify the potential causative gene mutation in a patient with UC associated with PSC and SSA
Whole exome sequencing (WES) is widely used to explore the genetic mechanism of rare diseases [18,19,20]. e present study investigated a patient with UC associated with PSC and SSA. e results on the inheritance of mutant genes may provide novel information regarding the pathological mechanism underlying this unusual condition
One male patient (63 years old) who was diagnosed with UC associated with PSC and SSA was included in the study

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Introduction

Patients diagnosed with ulcerative colitis (UC) associated with primary sclerosis cholangitis (PSC) and sessile serrated adenoma (SSA) are rare. e present study aimed to identify the potential causative gene mutation in a patient with UC associated with PSC and SSA. E present study aimed to identify the potential causative gene mutation in a patient with UC associated with PSC and SSA. Expression and diagnostic analysis of identified mutated genes was performed in the GSE119600 dataset (peripheral blood samples of PSC and UC) and GSE43841 dataset (tumor samples of SSA). A total of 842 single nucleotide variants (SNVs) in 728 genes were identified in the blood sample. Sanger sequence in blood revealed that the ITGB4 mutation was fully cosegregated with the result of WES in the patient. A variant, tumor protein p53 gene (TP53) (c.86delA; p.N29Tfs∗15) was identified in the tissue sample of SSA. E present study demonstrated that the ITGB4 (c.C2503G; p.P835A) and MUC3A (c.C1019T; p.P340L) mutations may be the potential causative variants in a patient with UC associated with PSC and SSA. Patients with PSC-IBD have an increased risk of colon cancer and cholangiocarcinoma compared with those with IBD alone [15]

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