Modeling multivariate age-related imaging variables with dependencies.

Neuroimaging techniques have been increasingly used to understand the neural biology of aging brains. The neuroimaging variables from distinct brain locations and modalities can exhibit age-related patterns that reflect localized neural decline. However, it is a challenge to identify the impacts of risk factors (eg, mental disorders) on multivariate imaging variables while simultaneously accounting for the dependence structure and nonlinear age trajectories using existing tools. We propose a mixed-effects model to address this challenge by building random effects based on the latent brain aging status. We develop computationally efficient algorithms to estimate the parameters of new random effects. The simulations show that our approach provides accurate parameter estimates, improves the inference efficiency, and reduces the root mean square error compared to existing methods. We further apply this method to the UK Biobank data to investigate the effects of tobacco smoking on the white matter integrity of the entire brain during aging and identify the adverse effects on white matter integrity with multiple fiber tracts.

Novel truncating variant of MN1 penultimate exon identified in a Chinese patient with newly recognized MN1 C-terminal truncation syndrome: Case report and literature review.

MN1 C-terminal truncation (MCTT) syndrome is a newly recognized neurodevelopmental disorder due to heterozygous gain-of-function C-terminal truncating mutations clustering in the last or penultimate exon of MN1 gene (MIM: 156100). Up to date, only 25 affected patients have been reported. Here, we report a 2-year-old Chinese girl with MCTT syndrome. The girl presented with the characteristic features of the syndrome, including global developmental delay (GDD), facial dysmorphism and hearing impairment. Notably, the patient did not have other frequently observed symptoms such as hypotonia, cranial or brain abnormalities, indicating variability of the phenotype of patients with MN1 C-terminal truncating mutations. Trio whole-exome sequencing revealed a novel de novo heterozygous nonsense variant in the extreme 3' region of penultimate exon of MN1 (NM_002430.3: c.3743G > A, p.Trp1248*). This rare truncating variant was classified as pathogenic due to its predicted gain-of-function effect, given that the gain-of-function MN1 truncating variants producing C-terminally truncated proteins have been confirmed to cause the recognizable syndrome. Additionally, a systematic review of previously reported MN1 variants including C-terminal truncating variants and N-terminal truncating variants shows that different location of MN1 truncating variants causes two distinct clinical subtypes. To our knowledge, this is the first reported case of MCTT syndrome caused by a novel MN1 C-terminal truncating variant in a Chinese population, which enriched the mutation spectrum of MN1 gene and further supporting the association of the novel MCTT syndrome with MN1 C-terminal truncating variants.

The clinical analysis of small supernumerary marker chromosomes in 17 children with mos 45,X/46,X,+mar karyotype.

Small supernumerary maker chromosome (sSMC) is a type of structurally abnormal chromosome. In order to identify the origin, morphology and other characteristics of sSMCs in children with mos 45,X/46,X,+mar karyotype, 17 patients (16 females and 1 male) were analyzed. All patients underwent general physical examination, gonadal imaging and molecular cytogenetic analyses, including Giemsa banding, dual-color fluorescence in situ hybridization and detection of the sex-determining region Y gene by polymerase chain reaction. Cytogenetic analyses indicated sSMCs in 14/17 cases were derived from the X chromosome, of which 8 individuals presented with ring-shaped sSMCs and 6 with centric minute-shaped sSMCs. The remaining 3 cases were derived from the Y chromosome, and all presented with minute-shaped sSMCs. All female patients exhibited short stature, gonadal dysgenesis and other typical features of Turner syndrome. The male patient exhibited short stature, hypospadias and bilateral cryptorchidism. In conclusion, the majority of the sSMCs in patients with a mos 45,X/46,X,+mar karyotype were derived from the sex chromosomes. The molecular cytogenetic features of sSMCs may provide useful information for genetic counseling, prenatal diagnosis and individualized treatment.

miR-590 regulates WT1 during proliferation of G401 cells.

Nephroblastoma (Wilms' tumor) is frequently associated with mortality in children. MicroRNAs (miRNAs) are important for tumor development serving as oncogenes or tumor suppressors. In the present study, miRNA­590 (miR­590) was identified to be upregulated in Wilms' tumor tissues compared with the normal adjacent tissues. Additionally, the levels of miR­590 were consistent with their clinical stage. Wilms' tumor 1 (WT1) was considered to be a tumor suppressor in certain tumor types, and it has been detected at low expression levels in various types of cancer with high cell proliferation and aggressive behavior. The expression levels of miR­590 were quantified using reverse transcription­quantitative polymerase chain reaction. Cell proliferation was measured using 5­ethynyl­20­deoxyuridine assays. The protein expression levels of WT1 were investigated by western blot analysis. To the best of our knowledge, the present study was the first to determine that WT1 was a target gene of miR­590 as miR­590 was able to negatively regulate WT1 expression level by binding to the specific target site within the 3'­untranslated region (3'­UTR) of WT1 in G401 cells. Additionally, overexpression of miR­590 promoted G401 cell proliferation which was consistent with the effect of small interfering RNA­WT1. Subsequently, the present study determined that the cell phenotype altered by miR­590 overexpression may be reversed by upregulation of WT1 in G401 cells. In conclusion, the observations indicated that miR­590 may function as an oncogene via targeting WT1 to induce G401 cell proliferation. These results may contribute to current understanding of the function of miR­590 in nephroblastoma.