Four novel germline mutations in the MLH1 and PMS2 mismatch repair genes in patients with hereditary nonpolyposis colorectal cancer

Background: Hereditary nonpolyposis colorectal cancer (HNPCC) is the most common cause of early onset hereditary colorectal cancer. In the majority of HNPCC families, microsatellite instability (MSI) and germline mutation in one of the DNA mismatch repair (MMR) genes are found. Materials and methods: The entire coding sequence of MMR genes (MLH1, MLH2, MLH6, and PMS2) was analyzed using direct sequencing. Also, tumor tests were done as MSI and immunohistochemistry testing. Results: We were able to find three novel MLH1 and one novel PMS2 germline mutations in three Iranian HNPCC patients. The first was a transversion mutation c.346A>C (T116P) and happened in the highly conserved HATPase-c region of MLH1 protein. The second was a transversion mutation c.736A>T (I246L), which caused an amino acid change of isoleucine to leucine. The third mutation (c.2145,6 delTG) was frameshift and resulted in an immature stop codon in five codons downstream. All of these three mutations were detected in the MLH1 gene. The other mutation was a transition mutation, c.676G>A (G207E), which has been found in exon six of the PMS2 gene and caused an amino acid change of glycine to glutamic acid. MSI assay revealed high instability in microsatellite for two patients and microsatellite stable for one patient. Conclusion: In all patients, an abnormal expression of the MMR proteins in HNPCC was related to the above novel mutation

Left ventricular strain rate for intraoperative evaluation of cardiac diastolic function by transesophageal echocardiography: the correlation between late diastolic peak longitudinal strain rate and the severity of diastolic dysfunction

Objectives: Speckle-tracking echocardiography is a promising tool for evaluating cardiac diastolic dysfunction. A correlation between left atrial strain rate during atrial contraction and the severity of diastolic dysfunction previously has been demonstrated. Because visualization of the left atrial walls is difficult with transesophageal echocardiography, the authors evaluated the use of left ventricular strain rate during atrial contraction as a substitute for left atrial strain rate to intraoperatively measure the extent of cardiac diastolic dysfunction. Design: Retrospective clinical study. Setting: Single institutional study. Participants: Sixty-six patients who underwent cardiac surgery between January 2018 and January 2021. Interventions: None. Measurements and main results: Preoperative echocardiographic reports and intraoperative echocardiographic images of the participants were studied. The correlation of cardiac diastolic dysfunction stage with the peak longitudinal strain rate during late diastole and the time to peak value were evaluated. The late diastolic peak longitudinal strain rate was correlated significantly with the stage of diastolic dysfunction (r = -0.64, p \u3c 0.0001). There was no significant correlation between the stage of diastolic dysfunction and the time to peak value (r = -0.17, p = 0.18). A late diastolic peak longitudinal strain rate \u3c0.68 1/s had a sensitivity of 80% and specificity of 81% for predicting grade 2 or 3 diastolic dysfunction. Conclusions: The late diastolic peak longitudinal strain rate correlates with the severity of diastolic dysfunction in patients undergoing cardiac surgery

Speckle- tracking echocardiography for the staging of diastolic dysfunction: the correlation between strain-based indices and the severity of left ventricular diastolic dysfunction

OBJECTIVES: Left ventricular diastolic function can be assessed by various methods. Tissue Doppler imaging is among the most commonly used techniques. However, this imaging is angle- dependent, affected by loading conditions, and susceptible to myocardial tethering. Speckle- tracking echocardiography also can measure strain-based indices to assess diastolic function, and it has fewer limitations than tissue Doppler imaging. Using speckle- tracking echocardiography, the authors evaluated the correlation between the stage of diastolic dysfunction and strain-based indices in patients undergoing cardiac surgery to determine whether strain-based indices can be used intraoperatively to identify the extent of left ventricular diastolic dysfunction. DESIGN: Retrospective clinical study. SETTING: Single university hospital. PARTICIPANTS: Fifty-eight patients undergoing cardiac surgery (December 2017 to December 2019). INTERVENTIONS: None. Measurement and Main Result: Preoperative echocardiographic reports and intraoperative echocardiographic images of the participants were studied. The correlation between the stage of left ventricular diastolic dysfunction and strain-based indices (including early diastolic peak longitudinal strain and tissue deceleration time) were evaluated. Early diastolic peak longitudinal strain rate significantly correlated with the stage of diastolic dysfunction (r = -0.7 and p \u3c 0.0001). Tissue deceleration time significantly correlated with the stage of diastolic dysfunction in patients with diastolic abnormality (r = -0.4 and p = 0.02). When patients with normal diastolic function were included, this correlation was not significant (r= -0.25 and p = 0.05). CONCLUSIONS: Intraoperatively measured early diastolic peak longitudinal strain rate and tissue deceleration time correlated with the severity of diastolic dysfunction in patients undergoing cardiac surgery