Huangmejia5030

We estimate a pathogenic variant carrier frequency of 1/1221 in the general and 1/155 in the Jewish Ashkenazi populations. Based on clinical, neuroimaging, and genetic data, we provide recommendations for variant reporting, clinical assessment, and surveillance/treatment of individuals with TECPR2-associated disorder. This sets the stage for future prospective natural history studies.The pioneering discovery research of X-linked intellectual disability (XLID) genes has benefitted thousands of individuals worldwide; however, approximately 30% of XLID families still remain unresolved. We postulated that noncoding variants that affect gene regulation or splicing may account for the lack of a genetic diagnosis in some cases. Detecting pathogenic, gene-regulatory variants with the same sensitivity and specificity as structural and coding variants is a major challenge for Mendelian disorders. Here, we describe three pedigrees with suggestive XLID where distinctive phenotypes associated with known genes guided the identification of three different noncoding variants. We used comprehensive structural, single-nucleotide, and repeat expansion analyses of genome sequencing. RNA-Seq from patient-derived cell lines, reverse-transcription polymerase chain reactions, Western blots, and reporter gene assays were used to confirm the functional effect of three fundamentally different classes of pathogenic noncoding variants a retrotransposon insertion, a novel intronic splice donor, and a canonical splice variant of an untranslated exon. In one family, we excluded a rare coding variant in ARX, a known XLID gene, in favor of a regulatory noncoding variant in OFD1 that correlated with the clinical phenotype. Our results underscore the value of genomic research on unresolved XLID families to aid novel, pathogenic noncoding variant discovery.Long noncoding RNAs (LncRNAs) regulate epithelial-mesenchymal transition (EMT). EMT involves myofibroblast differentiation and pulmonary fibrosis (PF). selleck chemical We aimed to determine the expression profiles of HOTAIR, CARLo-5, and CD99P1 LncRNAs in EMT-mediated myofibroblast differentiation in A549 cells and fibrotic human lungs and to explain their roles. A group of A549s was stimulated with transforming growth factor β (TGF-β; 5 ng/ml) to induce EMT. The remaining A549s were incubated with 20 μM FH535 after 24 h of TGF-β treatment to inhibit EMT. A549s were collected at 0, 24, 36, and 48 h. Expressions of three LncRNAs and protein/genes related to EMT, myofibroblast differentiation, and PF were assayed by quantitative reverse-transcription polymerase chain reaction and Western blot analysis in A549s and fibrotic human lungs. The targets of three LncRNAs were investigated by bioinformatics methods. TGF-β stimulation resulted in increased expressions of three LncRNAs, ACTA2, COL1A1, SNAI1, CTNNB1, TCF4, LEF1, α-SMA, and active-β-catenin, and decreased E-cadherin at 24, 36, and 48 h in A549s. FH535 treatment regressed these alterations. But it increased HOTAIR expression at 36 h and did not increase E-cadherin at 48 h. Fibrotic human lungs were characterized by increased expressions of HOTAIR, CARLo-5, CD99P1, and miR-214, decreased expressions of miR-148b, miR-218-1, miR-7-1, and the presence of CARLo-5 and CD99P1 in HDAC1-LncRNAs coprecipitation products, but not HOTAIR. Bioinformatic analysis showed the interactions of three LncRNAs with both proteins and at least 13 microRNAs related to EMT and PF. In conclusion, HOTAIR, CARLo-5, and CD99P1 can regulate EMT-mediated myofibroblast differentiation through interacting with proteins and miRNAs associated with EMT and PF. These LncRNAs can be considered as potential targets to decrease EMT for treating PF.Merkel cell carcinoma (MCC) is a rare but aggressive neuroendocrine carcinoma of the skin associated with Merkel cell polyomavirus and immunosuppression. Although MCC incidence is rising worldwide, MCC has not been sufficiently investigated in Japan. This study aimed to determine MCC demographics in Japan, including incidence, age, sex, location, spontaneous regression, and pure/combined MCC. Using PubMed and Igaku Chuo Zasshi, 847 MCC cases between 1985 and 2015 were extracted, and the main epidemiological characteristics were described. The mean age of all patients was 77.5 years. Regarding the characterized lesions, 63.0% were located on the head and neck, 5.2% on the trunk, 12.6% on the upper limb, 15.1% on the lower limb, 3.5% on the buttocks, and 0.6% on the genitals. Histopathological information regarding the presence of other malignancies could be retrieved in 611 cases, and a coexisting malignancy, mainly squamous cell carcinoma and Bowen's disease, was present in 14.2%. Subcutaneous MCC was observed in 31 patients with a male female ratio of 1.07 (16 men/15 women). Nodal lesions with unknown primary tumor location were described in 19 patients with a male female ratio of 0.9 (nine men/10 women) and a mean age of 77.7 years. Of 640 evaluable cases, spontaneous regression developed in 9.1%. Among those 58 patients, the male female ratio was 12.1 in 56 evaluable cases (18 men/38 women). Merkel cell polyomavirus was assessed in 180 patients, and the virus was detected in 31.1% and not detected in 68.9% of the patients. MCC is a rare disease in Japan, with incidence rates and male female ratios differing from those in the USA and European countries. Besides, this study reveals the high frequency of subcutaneous MCC and MCC with divergent differentiation patterns and spontaneous regression in Japan compared to other countries.

A standard MRI system phantom has been designed and fabricated to assess scanner performance, stability, comparability and assess the accuracy of quantitative relaxation time imaging. The phantom is unique in having traceability to the International System of Units, a high level of precision, and monitoring by a national metrology institute. Here, we describe the phantom design, construction, imaging protocols, and measurement of geometric distortion, resolution, slice profile, signal-to-noise ratio (SNR), proton-spin relaxation times, image uniformity and proton density.

The system phantom, designed by the International Society of Magnetic Resonance in Medicine ad hoc committee on Standards for Quantitative MR, is a 200 mm spherical structure that contains a 57-element fiducial array; two relaxation time arrays; a proton density/SNR array; resolution and slice-profile insets. Standard imaging protocols are presented, which provide rapid assessment of geometric distortion, image uniformity, T

and T

mapping, image resolution, slice profile, and SNR.