Search

To explore the clinical and genetic characteristics of three children with 22q13 deletion syndrome.Clinical data were collected and copy number variations in the patients and their parents were detected by using array-based comparative genomic hybridization (aCGH) and copy number variation sequencing (CNV-seq). The DECIPHER, ClinGen, OMIM, PubMed and Gene Review databases were retrieved for pathogenicity analysis.The common phenotypes of the three children have included variable global developmental delay, among which speech delay was the most obvious. Patient 1 had abnormalities of corpus callosum shown by magnetic resonance imaging. Patient 2 had dental crowding, pale skin, thick palms, hypotonia, and other facial features. Patient 3 had the mildest symptoms including language dysfunction, which has caught up with the development and improved significantly. All of the three children had harbored de novo deletions of 22q13.33q13.33 region, which spanned 0.84 Mb, 8.70 Mb and 0.90 Mb and involved 37, 126, and 34 genes, respectively.Above finding has enriched the clinical and genetic characteristics of 22q13 deletion syndrome and laid a foundation for genetic counseling and prenatal diagnosis.

Aimed at the problem of group data anomaly detection with no data labels, a k-nearest neighbor (kNN) algorithm is proposed to detect group data anomalies in the unsupervised mode. In order to reduce false negatives and false positives caused by the mutual interference between abnormal and normal values, a reverse k-nearest neighbor (RkNN) method is proposed to filter the abnormal group data in reverse. First, the RkNN algorithm uses statistical distance as the similarity measure between different groups of data. Then, the anomaly scores of each group and the initial abnormality are obtained by using the kNN algorithm. Finally, the initial abnormality is filtered by using the RkNN method. The experiment results show that the algorithm proposed can not only effectively reduce the false negatives and false positives, but also has a high anomaly detection rate and good stability.

Background Intellectual disability/developmental delay (ID/DD) is a kind of neurodevelopmental disorders of which the genetic etiologies are to be clarified in majority of the patients. The features of ID/DD patients with hemizygous variants in ATRX in China remains unclear due to the rare reports in worldwide.Methods Clinical data of six Chinese pedigrees with hemizygous variants in ATRX and ID/DD was collected. The information of physical examination, blood tests, metabolism screening of blood and urine, cranial magnetic resonance imaging (MRI), and whole exome sequencing (WES) of each patient was elaboratively analyzed.Result ID/DD patients with hemizygous variants in ATRX in China were characterized by moderate to profound ID/DD, facial malformations (microcephaly, hypertelorism, low nasal bridge and ear deformities), hypotonia and poor malmyelination. Five ARTX variants in six Chinese patients consisted of missense, in-frame deletion and frameshift variants, two of which were novel.Conclusion Six Chinese ID/DD patients were clinically and genetically diagnosed with ATRX mutations related syndrome (ATRX syndrome). And genotype–phenotype correlation was revealed in the participants, which expanded the clinical and genetic spectrum of ATRX syndrome.

Biotransformation is an effective technique to modify the structure and physicochemical properties of carbohydrates. In this work, Chinese yam (Dioscorea opposita Thunb.) starch was fermented by lactobacteria. The effect of fermentation time (6, 12, 30, 42 and 72 h) on structure and physicochemical properties of Chinese yam starch were investigated. The microstructure was destroyed after lactobacteria fermentation for 42 and 72 h. The X-ray diffraction pattern of Chinese yam starch indicated a transformed A to A + V crystalline type. → 4)-α-d-glucose-(1 → from backbone and unreduced terminal α-d-glucose-(1 → 4 from branch were identified by NMR spectra, and free glucose was only detected in fermented starch at 72 h. With the extension of fermentation time, the crystallinity and thermal parameters increased within 42 h and thereafter decreased. M

Hypomyelinating leukodystrophies (HLDs) are a rare group of heterogeneously genetic disorders characterized by persistent deficit of myelin observed on magnetic resonance imaging (MRI). To identify a new disease-associated gene of HLD, trio-based whole exome sequencing was performed for unexplained patients with HLD. Functional studies were performed to confirm the phenotypic effect of candidate protein variants. Two de novo heterozygous variants, c.227Tgt;G p.(L76R) or c.227Tgt;C p.(L76P) in

Genome sequencing(GS) has been applied in the diagnosis of global developmental delay(GDD)/intellectual disability(ID). However, the performance in those with inconclusive results from chromosomal microarray analysis(CMA) and exome sequencing(ES) is unknown. We recruited 100 pediatric GDD/ID patients from multiple sites in China from February 2018 to August 2020 for GS. Patients have received at least one genomic diagnostic test prior to enrollment. Reanalysis of CMA/ES data was performed. The yield of GS was calculated and explanations for missed diagnoses by CMA/ES were investigated. Clinical utility was assessed by interviewing the parents by phone. The overall diagnostic yield of GS was 23%. Seven families could have been solved with reanalysis of ES data. 13 families were missed by previous CMA/ES due to improper method. Three remained unsolved after ES reanalysis due to allele dropout, complex variants missed by ES, and a CNV in untranslated regions. Follow-up of the diagnosed families revealed that nine families experienced changes in clinical management, including identification of targeted treatments, cessation of unnecessary treatment, and considerations for family planning. GS demonstrated high diagnostic yield and clinical utility in this cohort of undiagnosed GDD/ID patients, detecting a wide range of variant types of different sizes in a single workflow.

Background Intellectual disability/developmental delay is a complex condition with extraordinary heterogeneity. A large proportion of patients lacks a specific diagnosis. Next generation sequencing, enabling identification of genetic variations in multiple genes, has become an efficient strategy for genetic analysis in intellectual disability/developmental delay. Methods Clinical data of 112 Chinese families with unexplained intellectual disability/developmental delay was collected. Targeted next generation sequencing of 454 genes related to intellectual disability/developmental delay was performed for all 112 index patients. Patients with promising variants and their other family members underwent Sanger sequencing to validate the authenticity and segregation of the variants. Results Fourteen promising variants in genes EFNB1, MECP2, ATRX, NAA10, ANKRD11, DHCR7, LAMA1, NFIX, UBE3A, ARID1B and PTPRD were identified in 11 of 112 patients (11/112, 9.82%). Of 14 variants, eight arose de novo, and 13 are novel. Nine patients (9/112, 8.03%) got definite molecular diagnoses. It is the first time to report variants in EFNB1, NAA10, DHCR7, LAMA1 and NFIX in Chinese intellectual disability/developmental delay patients and first report about variants in NAA10 and LAMA1 in affected individuals of Asian ancestry. Conclusions Targeted next generation sequencing of 454 genes is an effective test strategy for patients with unexplained intellectual disability/developmental delay. Genetic heterogenicity is significant in this Chinese cohort and de novo variants play an important role in the diagnosis. Findings of this study further delineate the corresponding phenotypes, expand the mutation spectrum and support the involvement of PTPRD in the disease. Electronic supplementary material The online version of this article (10.1186/s12881-019-0794-y) contains supplementary material, which is available to authorized users.

Among the hypomyelinating leukodystrophies, Pelizaeus–Merzbacher disease (PMD) is a representative disorder. The disease is caused by different types of PLP1 mutations, among which PLP1 duplication accounts for ~ 70% of the mutations. Previous studies have shown that PLP1 duplications lead to PLP1 retention in the endoplasmic reticulum (ER); in parallel, recent studies have demonstrated that PLP1 duplication can also lead to mitochondrial dysfunction. As such, the respective roles and interactions of the ER and mitochondria in the pathogenesis of PLP1 duplication are not clear. In both PLP1 patients’ and healthy fibroblasts, we measured mitochondrial respiration with a Seahorse XF Extracellular Analyzer and examined the interactions between the ER and mitochondria with super-resolution microscopy (spinning-disc pinhole-based structured illumination microscopy, SD-SIM). For the first time, we demonstrated that PLP1 duplication mutants had closer ER-mitochondrion interfaces mediated through structural and morphological changes in both the ER and mitochondria-associated membranes (MAMs). These changes in both the ER and mitochondria then led to mitochondrial dysfunction, as reported previously. This work highlights the roles of MAMs in bridging PLP1 expression in the ER and pathogenic dysfunction in mitochondria, providing novel insight into the pathogenicity of mitochondrial dysfunction resulting from PLP1 duplication. These findings suggest that interactions between the ER and mitochondria may underlie pathogenic mechanisms of hypomyelinating leukodystrophies diseases at the organelle level.

Hypomyelinating leukodystrophies (HLDs) are a rare group of disorders characterized by myelin deficit of the brain-based on MRI. Here, we studied 20 patients with unexplained HLD to uncover their genetic etiology through whole-exome sequencing (WES). Trio-based WES was performed for 20 unresolved HLDs families after genetic tests for the PLP1 duplication and a panel of 115 known leukodystrophy-related genes. Variants in both known genes that related to HLDs and promising candidate genes were analyzed. Minigene splicing assay was conducted to confirm the effect of splice region variant. All 20 patients were diagnosed with HLDs clinically based on myelin deficit on MRI and impaired motor ability. Through WES, in 11 of 20 trios, 15 causative variants were detected in seven genes TUBB4A, POLR1C, POLR3A, SOX10, TMEM106B, DEGS1, and TMEM63A. The last three genes have just been discovered. Of 15 variants, six were novel. Using minigene splicing assay, splice variant POLR3A c.1770 + 5 G > C was proved to disrupt the normal splicing of intron 13 and led to a premature stop codon at position 618 (p.(P591Vfs*28)). Our analysis determined the molecular diagnosis of 11 HLDs patients. It emphasizes the heterogenicity of HLDs, the diagnostic power of trio-based WES for HLDs. Comprehensive analysis including a focus on candidate genes helps to discover novel disease-causing genes, determine the diagnosis for the first time, and improve the yield of WES. Moreover, novel mutations identified in TUBB4A, POLR3A, and POLR1C expand the mutation spectrum of these genes.

Gene List. List of 454 genes related to ID/DD. (DOCX 13 kb)

BACKGROUND An increasing number of patients with chronic heart failure (CHF) are demanding more convenient and efficient modern health care systems, especially in remote areas away from central cities. Telehealth is receiving increasing attention, which may be useful to patients with CHF. OBJECTIVE This study aimed to evaluate the feasibility of a hospital-community-family (HCF)–based telehealth program, which was designed to implement remote hierarchical management in patients with CHF. METHODS This was a single-arm prospective study in which 70 patients with CHF participated in the HCF-based telehealth program for remote intervention for at least 4 months. The participants were recruited from the clinic and educated on the use of smart health tracking devices and mobile apps to collect and manually upload comprehensive data elements related to the risk of CHF self-care management. They were also instructed on how to use the remote platform and mobile app to send text messages, check notifications, and open video channels. The general practitioners viewed the index of each participant on the mobile app and provided primary care periodically, and cardiologists in the regional central hospital offered remote guidance, if necessary. The assessed outcomes included accomplishments of the program, usability and satisfaction, engagement with the intervention, and changes of heart failure–related health behaviors. RESULTS As of February 2018, a total of 66 individuals, aged 40-79 years, completed the 4-month study. Throughout the study period, 294 electronic medical records were formed on the remote monitoring service platform. In addition, a total of 89 remote consultations and 196 remote ward rounds were conducted. Participants indicated that they were generally satisfied with the intervention for its ease of use and usefulness. More than 91% (21/23) of physicians believed the program was effective, and 87% (20/23) of physicians stated that their professional knowledge could always be refreshed and enhanced through a library hosted on the platform and remote consultation. More than 60% (40/66) of participants showed good adherence to the care plan in the study period, and 79% (52/66) of patients maintained a consistent pattern of reporting and viewing their data over the course of the 4-month follow-up period. The program showed a positive effect on self-management for patients (healthy diet: P=.046, more fruit and vegetable intake: P=.02, weight monitoring: P=.002, blood pressure: PP=.049, and daily dosages of medicine taken: P=.006). CONCLUSIONS The HCF-based telehealth program is feasible and provided researchers with evidence of remote hierarchical management for patients with CHF, which can enhance participants’ and their families’ access and motivation to engage in self-management. Further prospective studies with a larger sample size are necessary to confirm the program’s effectiveness.

Summary form only given. High voltage circuit breakers utilize the very nature of rapid changing resistance of an electric arc to realize circuit interruption. High speed gas flow in a supersonic nozzle is normally used to ensure arc quenching in the chamber. The thermodynamic and electrical behaviors of arcs burning in such nozzles are closely related to the properties of the gaseous medium. SF 6 is currently used as working medium because of its excellent dielectric properties. However SF 6 is a strong greenhouse gas with a life time of 3200 years and a global warming potential (GWP) of 22800 in comparison with CO 2 which has a GWP of 1.01. The replacement of SF 6 with a more environmentally friendly gas is becoming an increasingly interesting research topic2 and practically important issue for power equipment manufacturers and network operators3.