Correlation between mild fetal ventriculomegaly, chromosomal abnormalities, and copy number variations.

BACKGROUND: Lateral ventriculomegaly is the most common abnormality of the fetal nervous system. This study investigated the incidence of chromosomal abnormalities and copy number variations (CNVs) in fetuses with mild ventriculomegaly (MV) based on various ultrasonic manifestations, identifying their corresponding features via ultrasound examination. METHODS: A retrospective analysis was performed on ultrasound and neurosonogram (NSG) manifestations and genetic profiles of 334 cases with MV and invasive prenatal diagnosis. RESULTS: Three hundred thirty-four cases with fetal MV were assessed via karyotyping. Further chromosomal microarray analysis (CMA) was performed in 182 cases with normal chromosome karyotypes; pathogenic chromosomal copy number variations (CNVs) were found in eight cases with a prevalence of 4.4% (8/182). In this study, the incidence rate of pathogenic abnormalities of chromosomes and CNVs was 5.7% (19/334). Based on whether lateral ventriculomegaly was complicated with other ultrasonic features, the 334 patients were divided into two groups: (1) 175 cases exhibited isolated ventriculomegaly (IVM; 52.4%, 175/334 group A) including two (1.1%, 2/175) with pathogenic chromosomal karyotype abnormalities-both trisomy 21; (2) 159 cases exhibited non-isolated ventriculomegaly (N-IVM; 47.6%, 159/334) with pathogenic chromosomal abnormalities and CNVs detected in17 cases (10.7%, 17/159). The N-IVM group was further divided into two groups: 105 cases exhibited MV with undetermined ultrasonic abnormalities (31.4%, 105/334, group B) with pathogenic chromosomal abnormalities and CNVs detected in eight cases (7.6%, 8/105); 54 cases exhibited MV with structural malformations (16.2%, 54/334, group C) of which nine cases (16.7%, 9/54) presented both pathogenic chromosomal abnormalities and CNVs, and five cases (55.6%, 5/9) were diagnosed with various cortical malformations. The pathogenicity rates of the IVM and N-IVM groups were statistically different (χ2=14.159, p = 0.000). There were significant differences (χ2=7.992, p = 0.005) among groups A, B, and C. CONCLUSIONS: Combinations of various ultrasonic abnormalities significantly affect the risk of pathogenic chromosomal abnormalities and CNVs in fetuses with MV. Cases involving cortical malformations require particular attention to the occurrence of pathogenic genetic abnormalities. When fetal MV is detected, a comprehensive ultrasound examination focusing on undetermined ultrasonic abnormalities is critical. Fetal NSG should be conducted to detect potential cerebral cortical malformation easily missed by routine ultrasound.

[Expression of Toll-like receptor 4 and tumor necrosis factor-α on peripheral-blood mononuclear cells and their correlation with myocardial perfusion in patients with diabetic cardiomyopathy].

OBJECTIVE: To explore the expression of Toll-like receptor 4 (TLR4) and tumor necrosis factor-α (TNF-α) on peripheral-blood mononuclear cells (PBMCs) and their correlation with myocardial perfusion in patients with diabetic cardiomyopathy (DCM). METHODS: The expression of TLR4 and TNF-α mRNA on PBMCs were examined by SYBR Green I real-time quantitative reverse transcription polymerase chain reaction (RT-PCR), the levels of TLR4 and TNF-α were examined by flow cytometric analysis and enzyme-linked immuno sorbent assay (ELISA) on DCM group (n = 20), Type 2 diabetic group (n = 22) and control group (n = 20). Myocardial perfusion was visualized by single-photon emission computed tomography (SPECT). RESULTS: The expressions of TLR4 and TNF-α mRNA/protein on PBMCs in DCM group were significantly higher than in Type 2 diabetic group, and higher in Type 2 diabetic group than in control groups (P < 0.05); summed stress score (SSS) and summed rest score (SRS) of myocardial perfusion in DCM group were significantly higher than in Type 2 diabetic group, and higher in Type 2 diabetic group than in control groups (P < 0.01). The expression of TLR4, TNF-α was positively correlated with SSS (r = 0.75, P < 0.05; r = 0.931, P < 0.005) and SRS (r = 0.78, P < 0.005; r = 0.789, P < 0.005). SSS and SRS in DCM group were also positively correlated with soluble vascular cell adhesion molecule-1 (sVCAM-1) (r = 0.728, P < 0.005; r = 0.738, P < 0.005) but there was no correlation between SSS and SRS and brain natriuretic peptide, LVEF, E/A, HbA1c, FBG, FIN and LDL-C (P > 0.05). CONCLUSION: The increased expression of TLR4 and TNF-α mRNA/protein on PBMCs and increased serum sVCAM-1 is linked with reduced myocardial perfusion in DCM group. TLR4 and TNF-α may thus play a critical role in the myocardial perfusion inflammation injury in these patients.