The diagnostic yield of intellectual disability: combined whole genome low-coverage sequencing and medical exome sequencing.

BACKGROUND: Intellectual disability (ID) is a heterogeneous neurodevelopmental disorder with a complex genetic underpinning in its etiology. Chromosome microarray (CMA) is recommended as the first-tier diagnostic test for ID due to high detection rate of copy number variation (CNV). METHODS: To identify an appropriate clinical detection scheme for ID in Han Chinese patients, whole genome low-coverage sequencing was performed as the first-tier diagnostic test, and medical exome sequencing (MES) as the second-tier diagnostic test for patients with negative results of CNVs. RESULTS: A total of 19 pathogenic CNVs in 16/95(16.84%) ID patients and 10 pathogenic single-nucleotide variations (SNVs), including 6 novel mutations in 8/95(8.42%) ID patients were identified on whom no pathogenic CNVs were discovered. The detection rate of CNVs in ID with multiple congenital anomalies (MCA) subgroup was significantly higher than ID with autism spectrum disorders and other IDs subgroups. And the single-nucleotide variations showed a higher occurrence rate in the other IDs subgroup. CONCLUSIONS: There were differences in the diagnostic yields of different variation types among the three ID subgroups. Our findings provided a new perspective on appropriate clinical detection scheme in different ID subgroups based on statistically significant differences among the three ID subgroups. The application of whole genome low-coverage sequencing as the first-tier diagnostic test for ID with MCA subgroup and MES as the first-tier diagnostic test for other ID subgroup was considered as an efficient clinical detection scheme.

Chromobox homolog 2 protein: A novel biomarker for predicting prognosis and Taxol sensitivity in patients with breast cancer.

Polycomb group (PcG) complexes modify histones to silence tumor suppressor genes, which exhibit an important function in tumorigenesis and progression. The chromobox (Cbx) protein family is a critical component of PcG-mediated repression. Cbx2, a member of the Cbx protein family, is hypothesized to exhibit a vital role in breast cancer. In the present study, immunohistochemical analysis using tissue microarrays was performed to determine the levels of Cbx2 protein expression in breast cancer. The association between Cbx2 expression and the clinical features and prognosis of 455 breast cancer patients was analyzed. In addition, the efficacy of Taxol was evaluated by comparing the survival of patients with high or low Cbx2 expression. The results revealed that Cbx2 expression was higher in cancer tissues compared with adjacent normal tissues. Furthermore, high Cbx2 expression was significantly associated with large tumor size, lymph node metastasis, high TNM stage and positive human epidermal growth factor receptor-2 (HER-2) status. Patients with high Cbx2 expression also exhibited a shorter mean overall survival (OS) time (74.37 months) compared with patients with low Cbx2 expression (77.37 months). Univariate analysis indicated that high Cbx2 expression increased the risk of mortality by 1.826-fold compared with low Cbx2 expression [hazard ratio (HR), 1.826; 95% confidence interval (CI), 1.069-3.116; P=0.027]. Among patients with high Cbx2 expression, the mean OS time of individuals treated with Taxol (71.01 months) was lower compared with patients that had not received Taxol treatment (78.43 months; log-rank test statistic, 13.03; P<0.001). However, no significant difference in OS time was identified in the low expression group. The results of the current study revealed that Cbx2 may present a novel biomarker for predicting the prognosis of breast cancer patients. Cbx2 may also represent a potential target for treatment due to its important function in Taxol treatment responses.

The potential of plasma miRNAs for diagnosis and risk estimation of colorectal cancer.

Circulating microRNAs (miRNAs) were recognized to be potential non-invasive biomarkers for colorectal cancer (CRC) detection and prediction. Meanwhile, the association of the expression of plasma miRNAs with the risk of CRC patients has rarely been analyzed. Therefore, we conducted this study to evaluate the value of plasma miRNAs for CRC diagnosis and risk estimation. Fasting blood samples from 100 CRC patients and 79 cancer-free controls were collected. Plasma miR-106a, miR-20a, miR-27b, miR-92a and miR-29a levels were detected by RT-qPCR. Sensitivity and specificity were employed to evaluate the diagnostic value of miRNAs for CRC. Univariate and multivariate logistic regression were employed to analyze the association between miRNAs expression and CRC risk. As results, miR-106a and miR-20a were elevated in the patients with CRC. The sensitivity of miR-106a was 74.00% and the specificity was 44.40%, while the cutoff value was 2.03. As for miR-20a, the sensitivity was 46.00% and specificity was 73.42% when employed 2.44 as cutoff value. High expression of plasma miR-106a increased CRC risk by 1.80 -fold. Plasma miR-106a and miR-20a may as noninvasive biomarkers for detecting the CRC. High expression of miR-106a associated with CRC risk.