scholarly journals Discovering Genotype Variants in an Infant with VACTERL through Clinical Exome Sequencing: A Support for Personalized Risk Assessment and Disease Prevention

2021 ◽  
Vol 13 (1) ◽  
pp. 45-56
Author(s):  
Gloria Pelizzo ◽  
Luigi Chiricosta ◽  
Emanuela Mazzon ◽  
Gian Vincenzo Zuccotti ◽  
Maria Antonietta Avanzini ◽  
...  

Congenital anomalies may have an increased risk of noncommunicable diseases (NCDs) We performed a clinical exome analysis in an infant affected by “Vertebral, Anorectal, Cardiac, Tracheoesophageal, Genitourinary, and Limb” (VACTERL) malformation association to identify potential biomarkers that may be helpful for preventing malignancy risk or other chronic processes. Among the variants, six variants that may be linked with VACTERL were identified in the exome analysis. The variants c.501G>C on OLR1 and c.-8C>G on PSMA6 were previously associated with myocardial infarction. The variants c.1936A>G on AKAP10 and c.575A>G on PON1 are linked to defects in cardiac conduction and artery disease, respectively. Alterations in metabolism were also suggested by the variants c.860G>A on EPHX2 and c.214C>A on GHRL. In addition, three variants associated with colon cancer were discovered. Specifically, the reported variants were c.723G>A on CCND1 and c.91T>A on AURKA proto-oncogenes as well as c.827A>C in the tumor suppressor PTPRJ. A further inspection identified 15 rare variants carried by cancer genes. Specifically, these mutations are located on five tumor suppressors (SDHA, RB1CC1, PTCH1, DMBT1, BCR) and eight proto-oncogenes (MERTK, CSF1R, MYB, ROS1, PCM1, FGFR2, MYH11, BRCC3) and have an allele frequency lower than 0.01 in the Genome Aggregation Database (GnomAD). We observed that the cardiac and metabolic phenotypic traits are linked with the genotype of the patient. In addition, the risk of developing neoplasia cannot be excluded a priori. Long-term surgical issues of patients with VATER syndrome could benefit from the clinical exome sequencing of a personalized risk assessment for the appearance of further disease in pubertal timing and adult age.

2020 ◽  
Vol 29 (4) ◽  
pp. 598-606
Author(s):  
Maegan E. Roberts ◽  
Lisa R. Susswein ◽  
Wanchun Janice Cheng ◽  
Natalie J. Carter ◽  
Amber C. Carter ◽  
...  

Kardiologiia ◽  
2015 ◽  
Vol 3_2015 ◽  
pp. 75-84 ◽  
Author(s):  
I.V. Druk Druk ◽  
G.I. Nechaeva Nechaeva ◽  
O.V. Oseeva Oseeva ◽  
E.G. Pomorgajlo Pomorgajlo ◽  
V.N. Maksimov Maksimov ◽  
...  

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Xifeng Wu ◽  
Chi Pang Wen ◽  
Yuanqing Ye ◽  
MinKwang Tsai ◽  
Christopher Wen ◽  
...  

An amendment to this paper has been published and can be accessed via a link at the top of the paper.


2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Jure Knez ◽  
Monika Sobocan ◽  
Urska Belak ◽  
Rajko Kavalar ◽  
Mateja Zupin ◽  
...  

Abstract Background The aim of this study was to evaluate changes in prognostic risk profiles of women with endometrial cancer by comparing the clinical risk assessment with the integrated molecular risk assessment profiling. Patients and methods This prospective study recruited patients with biopsy proven endometrial cancer treated at the University Medical Centre Maribor between January 2020 to February 2021. Patient clinical data was assessed and categorized according to the currently valid European Society of Gynaecological Oncology, European SocieTy for Radiotherapy and Oncology, and European Society of Pathology (ESGO/ESTRO/ESP) guidelines on endometrial cancer. Molecular tumour characterization included determination of exonuclease domain of DNA polymerase-epsilon (POLE) mutational status by Sanger sequencing and imunohistochemical specimen evaluation on the presence of mismatch repair deficiencies (MMRd) and p53 abnormalities (p53abn). Results Fourty-five women were included in the study. Twenty-two tumours were of non-specific mutational profile (NSMP) (56.4%), 13 were classified as MMRd (33.3%), 3 were classified as p53abn (7.7%) and 1 was classified as POLE mutated (2.6%). Six tumours (15.4%) had multiple molecular classifiers, these were studied separately and were not included in the risk assessment. The clinical risk-assessment classified 21 women (53.8%) as low-risk, 5 women (12.8%) as intermediate risk, 2 women as high-intermediate risk (5.1%), 10 women (25.6%) as high risk and 1 patient as advanced metastatic (2.6%). The integrated molecular classification changed risk for 4 women (10.3%). Conclusions Integrated molecular risk improves personalized risk assessment in endometrial cancer and could potentially improve therapeutic precision. Further molecular stratification with biomarkers is especially needed in the NSMP group to improve personalized risk-assessment.


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