Highly Efficient Red/Near-Infrared Phosphorescence from Doped Crystals.

Organic red/near-infrared (NIR) room temperature phosphorescence (RTP) materials with low toxicity and facile synthesis are highly sought after, particularly for applications in biotechnology and encryption. However, achieving efficient red/NIR RTP emitters has been challenging due to the weak spin-orbit coupling of organics and the rapid nonradiative decay imposed by the energy gap law. Here we demonstrate highly efficient red/NIR RTP with boosted quantum yields (Φps) of up to 32.96 % through doping the thionated derivatives of phthalimide (PAI) (MTPAI and DTPAI) into PAI crystals. The red-shifted photoluminescence (PL) stems from a combination of the external heavy atom effect and the formation of emissive clusters centered around electron-rich sulfur atoms. Furthermore, the dopants enhance exciton generation efficiency and facilitate energy transfer from smaller PAI units to larger aggregates, leading to dramatically increased Φp. This strategy proves universal, opening possibilities for acquiring long-wavelength RTP with tunable photophysical properties. The doped crystals exhibit promising applications in optical waveguides and encryption paper/ink. This research provides a practical approach to obtaining long-wavelength RTP materials and offers valuable insights into the mechanisms governing host-guest systems.

Photochromic luminescence of organic crystals arising from subtle molecular rearrangement.

Photoluminescence (PL) colour-changing materials in response to photostimulus play an increasingly significant role in intelligent applications for their programmability. Nevertheless, current research mainly focuses on photochemical processes, with less attention to PL transformation through uniform aggregation mode adjustment. Here we show photochromic luminescence in organic crystals (e.g. dimethyl terephthalate) with PL varying from dark blue to purple, then to bright orange-red, and finally to red. This change is attributed to the emergence of clusters with red emission, which is barely achieved in single-benzene-based structures, thanks to the subtle molecular rearrangements prompted by light. Crucial to this process are the through-space electron interactions among molecules and moderate short contacts between ester groups. The irradiated crystals exhibit reversible PL transformation upon sufficient relaxation, showing promising applications in information storage and smart optoelectronic devices. This research contributes to the development of smart photochromic luminescent materials with significant PL colour transformations through molecular rearrangement.

Co-crystallization and Clustering Afforded Simultaneously Boosted Efficiency, Lifetime, and Color Tunability of Organic Afterglows.

Pure organic persistent room-temperature phosphorescence (p-RTP) is in urgent demand for advanced optoelectronic and bioelectronic applications. However, it remains an enormous challenge to modulate the emission colors while simultaneously boosting the phosphorescence lifetimes and efficiencies. Herein, we report the co-crystallization between melamine and cyclic imide-based non-conventional luminophores, which affords co-crystals owning multiple hydrogen bonds and effective clustering of electron-rich units, thus resulting in diverse emissive species with highly rigidified conformations and promoted spin-orbit coupling. Consequently, p-RTP co-crystals with simultaneously enhanced efficiencies and lifetimes of up to 12.0% and 898 ms, alongside remarkably improved color tunability, are obtained. These results may spur the future rational design of high-performance p-RTP materials and advance the mechanism of understanding of the origin of color-tunable phosphorescence.

Genetic Diseases and Invasive Infections in Infants 100 Days or Younger.

BACKGROUND: Understanding the association of genetic diseases with invasive infections in neonates or infants is important, given the clinical and public health implications of genetic diseases. METHODS: We conducted a retrospective case-control study over a 5-year period to investigate the association between genetic diseases and invasive infections in neonates or infants. The case group included 56 patients with laboratory-confirmed invasive infections and a genetic etiology identified by exome sequencing. Another 155 patients without a genetic etiology were selected as controls from the same pool of patients. RESULTS: An overview of genetic diseases that predispose patients to develop invasive infections were outlined. We identified 7 independent predictors for genetic conditions, including prenatal findings [adjusted odds ratio (aOR), 38.44; 95% confidence interval (CI): 3.94-374.92], neonatal intensive care unit admission (aOR, 46.87; 95% CI: 6.30-348.93), invasive ventilation (aOR, 6.66; 95% CI: 3.07-14.46), bacterial infections (aOR, 0.21; 95% CI: 0.06-0.69), fever (aOR, 0.15; 95% CI: 0.08-0.30), anemia (aOR, 6.64; 95% CI: 3.02-14.59) and neutrophilia (aOR, 0.98; 95% CI: 0.96-0.99). The area under the curve for the predictive model was 0.921 (95% CI: 0.876-0.954). We also found that a genetic etiology [hazard ratio (HR), 7.25; 95% CI: 1.71-30.81], neurological manifestations (HR, 3.56; 95% CI: 1.29-9.88) and septic shock (HR, 13.83; 95% CI: 3.18-60.10) were associated with severe outcomes. CONCLUSIONS: Our study established predictive variables and risk factors for an underlying genetic etiology and its mortality in neonates or infants with invasive infections. These findings could lead to risk-directed screening and treatment strategies, which may improve patient outcomes.

RASopathies due to de novo pathogenic variants: clinical features, genetic findings and outcomes in nine neonates born with congenital heart defects.

BACKGROUND: There are limited information available related to neonatal characteristics of RASopathies, a group of autosomal dominant syndromes with considerable phenotypic overlap. METHODS: The retrospective review revealed 9 neonates born with congenital heart defects (CHDs) and diagnosed as RASopathies due to de novo mutations (DNMs) by trio-based exome sequencing (ES) between January 2017 and December 2020. We report in details of the neonatal course, molecular analysis and 180-days of age follow-up in affected individuals. RESULTS: The early clinical spectrum included various types of CHDs, less noticeable multiple extracardiac anomalies and unspecific symptoms like poor feeding. Of the 8 variants identified from 6 genes, 2 in RASA1 were novel: (NM_002890.2: c.2828 T > C (p.Leu943Pro)) and (NM_002890.2: c.2001del (p.Pro668Leufs*10)), which functionally impaired the protein structure. There was a relatively high mortality rate of 33.33% (3/9) for all the defects combined. A RAF1-deficient male and a RASA1-deficient male survived from severe heart failure by surgical interventions in early life. CONCLUSIONS: Our results revealed that family-based ES was useful in identifying DNMs and causal genes for sporadic diseases and screening Rasopathies shortly after birth. We recommended a family-based ES and a full phenotypic evaluation including echocardiogram, magnetic resonance imaging, ultrasonography and coagulation screening in neonates with CHDs and a suspected genetic etiology.

Comparative Transcriptome Analysis Provides Insights Into the Mechanism by Which 2,4-Dichlorophenoxyacetic Acid Improves Thermotolerance in Lentinula edodes.

As the widest cultivated edible mushroom worldwide, Lentinula edodes suffers serious yield and quality losses from heat stress during growth and development, and in our previous study, exogenous 2,4-Dichlorophenoxyacetic acid (2,4-D) was found to improve the thermotolerance of L. edodes strain YS3357, but the molecular mechanism remains unclear. Here, we explored the potential protective mechanism of exogenous 2,4-D against heat stress by transcriptome analysis. 2,4-D possible improve the thermotolerance of L. edodes through regulating antioxidant genes, transcription factors, energy-provision system, membrane fluidity, and cell wall remodeling. Furthermore, 2,4-D was also found to regulate the saturation levels of fatty acids and ATP content in L. edodes mycelium under heat stress. This study proposed a regulatory network of 2,4-D in regulating L. edodes response to heat stress, providing a theoretical basis for improving L. edodes thermotolerance, and facilitating the understanding of the molecular mechanism of exogenous hormones in alleviating abiotic stress damage to macrofungi.

Accessing Excitation- and Time-Responsive Afterglows from Aqueous Processable Amorphous Polymer Films through Doping and Energy Transfer.

Smart afterglow materials in response to excitation and delay time, including crystals, polymeric films, and carbon dots, have attracted considerable attention on account of their fundamental value in photophysics and promising applications in optoelectronics. However, the fabrication of amorphous and flexible polymer films with fine control remains underexplored. Herein, new doped polymer films based on sodium alginate and aromatic carboxylates are developed, which demonstrate following advantages: (i) easy and fast fabrication through the aqueous solution process, (ii) flexible, transparent, and re-dissolvable characteristics, (iii) multi-tunable afterglow colors from blue to red and even white with fine control. Specifically, even better controllability can be achieved through co-doping and triplet-to-singlet Förster resonance energy transfer (TS-FRET). Multimode advanced anti-counterfeiting of these materials is demonstrated using their excitation- and time-dependent as well as TS-FRET-mediated afterglow colors.

Clustering and halogen effects enabled red/near-infrared room temperature phosphorescence from aliphatic cyclic imides.

Pure organic room temperature phosphorescence (RTP) materials become increasingly important in advanced optoelectronic and bioelectronic applications. Current phosphors based on small aromatic molecules show emission characteristics generally limited to short wavelengths. It remains an enormous challenge to achieve red and near-infrared (NIR) RTP, particularly for those from nonaromatics. Here we demonstrate that succinimide derived cyclic imides can emit RTP in the red (665, 690 nm) and NIR (745 nm) spectral range with high efficiencies of up to 9.2%. Despite their rather limited molecular conjugations, their unique emission stems from the presence of the imide unit and heavy atoms, effective molecular clustering, and the electron delocalization of halogens. We further demonstrate that the presence of heavy atoms like halogen or chalcogen atoms in these systems is important to facilitate intersystem crossing as well as to extend through-space conjugation and to enable rigidified conformations. This universal strategy paves the way to the design of nonconventional luminophores with long wavelength emission and for emerging applications.

Nonconventional luminophores: characteristics, advancements and perspectives.

Nonconventional luminophores devoid of remarkable conjugates have attracted considerable attention due to their unique luminescence behaviors, updated luminescence mechanism of organics and promising applications in optoelectronic, biological and medical fields. Unlike classic luminogens consisting of molecular segments with greatly extended electron delocalization, these unorthodox luminophores generally possess nonconjugated structures based on subgroups such as ether (-O-), hydroxyl (-OH), halogens, carbonyl (CO), carboxyl (-COOH), cyano (CN), thioether (-S-), sulfoxide (SO), sulfone (OSO), phosphate, and aliphatic amine, as well as their grouped functionalities like amide, imide, anhydride and ureido. They can exhibit intriguing intrinsic luminescence, generally featuring concentration-enhanced emission, aggregation-induced emission, excitation-dependent luminescence and prevailing phosphorescence. Herein, we review the recent progress in exploring these nonconventional luminophores and discuss the current challenges and future perspectives. Notably, different mechanisms are reviewed and the clustering-triggered emission (CTE) mechanism is highlighted, which emphasizes the clustering of the above mentioned electron rich moieties and consequent electron delocalization along with conformation rigidification. The CTE mechanism seems widely applicable for diversified natural, synthetic and supramolecular systems.

Gene expression profiles in the brain of phenylketonuria mouse model reversed by the low phenylalanine diet therapy.

To gain insight into the potential protective mechanisms of low phenylalanine diet (LPD) in phenylketonuria (PKU), gene expression profiles were studied in the cerebral cortex and hippocampus of a PKU mouse model (BTBR-Pahenu2). PKU mice were fed with low Phe diet (LPD-PKU group) and normal diet (PKU group). Wild-type mice were treated with normal diet (WT group) as control. After 12 weeks, we detected gene expression in the cerebral cortex and hippocampus of the three groups by RNA-sequencing, and then screened the differentially-expressed genes (DEGs) among the groups by bioinformatics analyses. We found that the transcriptional profiles of both cerebral cortex and hippocampus changed markedly between PKU and WT mice. Furthermore, LPD changed the transcriptional profiles of the cerebral cortex and the hippocampus of PKU mice significantly, especially in the cerebral cortex, with overlaps of genes that changed with the disease and altered by LPD treatment. In the cerebral cortex, hundreds of DEGs enriched in a wide spectrum of biological processes, molecular function, and cellular component, including nervous system development, axon development and guidance, calcium ion binding, modulation of chemical synaptic transmission, and regulation of protein kinase activity. In the hippocampus, the overlapping genes were enriched in positive regulation of long term synaptic, negative regulation of excitatory postsynaptic potential, positive regulation of synapse assembly. Our results showed that genes impaired in PKU and then rescued by LPD might indicate the potential protective capability of LPD in the PKU brain.

Primary immunodeficiency-related genes in neonatal intensive care unit patients with various genetic immune abnormalities: a multicentre study in China.

OBJECTIVES: The present phenotype-based disease classification causes ambiguity in diagnosing and determining timely, effective treatment options for primary immunodeficiency (PID). In this study, we aimed to examine the characteristics of early-onset PID and proposed a JAK-STATopathy subgroup based on their molecular defects. METHODS: We reviewed 72 patients (< 100 days) retrospectively. These patients exhibited various immune-related phenotypes and received a definitive molecular diagnosis by next-generation sequencing (NGS)-based tests. We evaluated the PID-causing genes and clinical parameters. We assessed the genes that shared the JAK-STAT signalling pathway. We also examined the potential high risks related to the 180-day death rate. RESULTS: We identified PID disorders in 25 patients (34.72%, 25/72). The 180-day mortality was 26.39% (19/72). Early onset of disease (cut-off value of 3.5 days of age) was associated with a high 180-day death rate (P = 0.009). Combined immunodeficiency with associated or syndromic features comprised the most common PID class (60.00%, 15/25). Patients who presented life-threatening infections were most likely to exhibit PID (odds ratio [OR] = 2.864; 95% confidence interval [CI]: 1.047-7.836). Twelve out of 72 patients shared JAK-STAT pathway defects. Seven JAK-STATopathy patients were categorised as PID. They were admitted to NICUs as immunological emergencies. Most of them experienced severe infections and thrombocytopenia, with 4 succumbing to an early death. CONCLUSIONS: This study confirmed that NGS can be utilised as an aetiological diagnostic method of complex immune-related conditions in early life. Through the classification of PID as pathway-based subtypes, we see an opportunity to dissect the heterogeneity and to direct targeted therapies.

Application of Next-Generation Sequencing for Genetic Diagnosis in Neonatal Intensive Care Units: Results of a Multicenter Study in China.

To identify next-generation-sequencing (NGS) clinical usability and to propose a standard diagnostic routine for critically ill infants, aged less than 100 days and suspected of having a genetically heterogeneous condition, a retrospective study was conducted between January 2016 and December 2018 at neonatal intensive care units (NICUs) of three tertiary hospitals in Shanghai, China. Whole-exome sequencing (WES) or panel sequencing was performed on 307 patients. Trio-WES, trio-panel, proband-WES, and proband-panel diagnostic yields were 39.71% (83/209), 68.75% (22/32), 59.09% (26/44), and 33.33% (4/12), respectively. Definitive molecular diagnoses of 142 infants (46.25%) uncovered 99 disorders; 21 disorders displayed on 44.37% of the diagnosed patients. Genetic etiologies were identified for 61.73% (50/81) of the deceased infants. One in three (29.58%) diagnosed infants exhibited one of the following four clinical traits which had a higher odds of diagnostic rate: integument abnormality (adjusted odds ratio [aOR], 19.7; 95% confidence interval [CI], 2.5-156.3), complex immune-related phenotypes (aOR, 9.2; 95% CI, 1.4-83.5), mixed nervous system phenotypes and congenital anomalies (aOR, 5.0; 95% CI, 1.3-19.1), or mixed metabolism and nervous system phenotypes (aOR, 4.5; 95% CI, 1.0-21.5). Our results demonstrated that NGS was an effective diagnostic tool. Infants exhibiting integument, complex immune-related conditions, metabolism, and nervous signs have higher chances of carrying variants in known disease-causing genes. The number of specific phenotypes could be used as an independent predictor of a positive molecular diagnosis, rather than an isolated abnormality. We developed a molecular diagnostic procedure for the use of NGS for diagnosis in Chinese NICU population based on individual characteristics.

Effective Internal and External Modulation of Nontraditional Intrinsic Luminescence.

The rational modulation of the nontraditional intrinsic luminescence (NTIL) of nonconventional luminophores remains difficult, on account of the limited understanding on the structure-property relationships and emission mechanisms. Herein, the effective modulation of NTIL is demonstrated based on a group of nonaromatic anhydrides and imides. Mutual bridging of isolated subgroups effectively promotes intramolecular through-space conjugation (TSC), leading to red-shifted emission, enhanced efficiency, and prolonged persistent room-temperature phosphorescence (p-RTP). The substitution of heteroatoms from oxygen to nitrogen drastically changes the TSC and enhances intermolecular interactions, resulting in enhanced emission efficiency. In addition, upon freezing, compression, or embedding into polymer matrices, the emission intensity and color remain well regulated. These results shed new light on the rational modulation of the NTIL and p-RTP of nonconventional luminophores.

Color-Tunable, Excitation-Dependent, and Time-Dependent Afterglows from Pure Organic Amorphous Polymers.

Achieving persistent room-temperature phosphorescence (p-RTP), particularly those of tunable full-colors, from pure organic amorphous polymers is attractive but challenging. Particularly, those with tunable multicolor p-RTP in response to excitation wavelength and time are highly important but both fundamentally and technically underexplored. Here, a facile and general strategy toward color-tunable p-RTP from blue to orange-red based on amidation grafting of luminophores onto sodium alginate (SA) chains, resulting in amorphous polymers with distinct p-RTP and even impressively excitation-dependent and time-dependent afterglows is reported. p-RTP is associated with the unique semi-rigidified SA chains, effective hydrogen bonding network, and oxygen barrier properties of SA, whereas excitation-dependent and time-dependent afterglows should stem from the formation of diversified p-RTP emissive species with comparable but different lifetimes. These results outline a rational strategy toward amorphous smart luminophores with colorful, excitation-dependent, and time-dependent p-RTP, excellent solution processability, and film-forming ability for versatile applications.

The Application of Next-Generation Sequencing (NGS) in Neonatal-Onset Urea Cycle Disorders (UCDs): Clinical Course, Metabolomic Profiling, and Genetic Findings in Nine Chinese Hyperammonemia Patients.

During Jan. 2016-Dec. 2019, nine Chinese patients from eight unrelated families were diagnosed with neonatal-onset UCDs by targeted panel sequencing or whole-exome sequencing (WES). Their clinical manifestations, biochemical features, 180-day-age outcomes, and molecular genetic characteristics were reviewed retrospectively. NGS-based tests revealed 7 patients diagnosed with ornithine transcarbamylase deficiency (OTCD) and 2 with carbamoylphosphate synthetase I deficiency (CPS1D). The spectrum of the clinical presentation of nine affected individuals progressed from unspecific symptoms like poor feeding to somnolence, coma, and death. All patients presented with an acute hyperammonemia. The most robust metabolic pattern in OTCD was hyperglutaminemic hyperammonemia with high concentration of urine orotic acid, and it was reported in six patients. Of ten variants found on the OTC gene and CPS1 gene, 3 were novel: (c.176T>C (p.L59P)) in the OTC gene, c.2938G>A (p.G980S) and c.3734T>A (p.L1245H) in the CPS1 gene. There was a high mortality rate of 77.78% (7/9) for all the defects combined. An OTC-deficient male and a CPS1-deficient female survived from episodes of hyperammonemia. Although prompt recognition of UCD and the use of alternative pathway therapy in addition to provision of appropriate nutrition and dialysis improved survival, the overall outcomes for the neonatal-onset type are poor in China.

Accessing Tunable Afterglows from Highly Twisted Nonaromatic Organic AIEgens via Effective Through-Space Conjugation.

Nonaromatic, cross-conjugated, and highly twisted luminogens consisting of acylated succinimides demonstrate aggregation-induced emission characteristics along with tunable multicolor photoluminescence and afterglows in their single crystals. Effective through-space conjugation among different moieties bearing n/π electrons promote the spin-orbit coupling and intersystem crossing and lead to diverse emissive clusters with concurrently rigidified conformations, thus allowing readily tunable emissions. Derived from it, the proof-of-concept application for advanced anti-counterfeiting is illustrated. These results should spur the rational design of novel nonaromatic AIEgens, and moreover advance understandings of the non-traditional intrinsic luminescence and the origin of tunable multicolor afterglows.

Sparse Manifold-Regularized Neural Networks for Polarimetric SAR Terrain Classification.

In this article, a new deep neural network based on sparse filtering and manifold regularization (DSMR) is proposed for feature extraction and classification of polarimetric synthetic aperture radar (PolSAR) data. DSMR uses a novel deep neural network (DNN) to automatically learn features from raw SAR data. During preprocessing, the spatial information between pixels on PolSAR images is exploited to weight each data sample. Then, in the pretraining and fine-tuning, DSMR uses the population sparsity and the lifetime sparsity (dual sparsity) to learn the global features and preserves the local structure of data by neighborhood-based manifold regularization. The dual sparsity only needs to tune a few parameters, and the manifold regularization cuts down the number of training samples. Experimental results on synthesized and real PolSAR data sets from different SAR systems show that DSMR can improve classification accuracy compared with conventional DNNs, even for data sets with a large angle of incidence.

Examining the blood amino acid status in pretherapeutic patients with hyperphenylalaninemia.

BACKGROUND: Hyperphenylalaninemia is the most common genetic metabolic disease. Early treatment prevents brain injury effectively. The present study aimed to detect the exact amino acid status of patients with hyperphenylalaninemia before treatment. METHODS: Data of 116 newborn patients from our Newborn Screening Center and 161 older patients from our clinic before treatment were collected. The content of 17 amino acids in their blood was determined by tandem mass spectrometry and compared with normal controls. Relationship between phenylalanine and other amino acids in patients was analyzed using the smoothing curve fitting and threshold effect analysis. RESULTS: Most amino acids in the blood of patients were within the normal range; however, they were different significantly from those of the normal children. Newborn patients showed higher phenylalanine (346.30 vs 45.90 µmol/L), valine (121.50 vs 110.30 µmol/L), citrulline, ornithine and lower tyrosine (52.97 vs 66.12 µmol/L), threonine (68.68 vs 78.21 µmol/L), glutamine levels than observed in normal newborns. Older patients showed significantly higher phenylalanine (844.00 vs 51.82 µmol/L), valine (117.60 vs 110.90 µmol/L), histidine, serine and lower tyrosine (55.97 vs 67.31 µmol/L), threonine (35.94 vs 51.89 µmol/L), alanine, asparagine, glutamic acid, methionine, arginine, glycine, ornithine, glutamine content than found in matched normal children. Tyrosine, valine, ornithine, and threonine in newborn patients and tyrosine, glycine, glutamine, and threonine in older patients had a nonlinear correlation with phenylalanine levels with obvious threshold effect and clear inflection points. CONCLUSION: Significant difference was observed in the amino acid status between pretherapeutic hyperphenylalaninemia patients and normal children. Some amino acids showed notable threshold effect with phenylalanine level in a nonlinear pattern.

Amphiphilic Polymer-Mediated Aggregation-Induced Emission Nanoparticles for Highly Sensitive Organophosphorus Pesticide Biosensing.

Biosensing applications require signal reporters to be sufficiently stable and biosafe as well as highly efficient. Aggregation-induced emission (AIE) nanoparticles have proven to be capable of cell-imaging and cancer therapy; however, realizing sensitive detection of biomolecules remains a great challenge because of their instability, biotoxicity, and lack of modifiable functional groups. Herein, we report a self-assembling strategy to fabricate AIE nanoparticles (PTDNPs) through the dispersion of amphiphilic polymers (PTDs) in phosphate-buffered saline. The PTDs were prepared through radical copolymerization of N-(1,2,2-triphenylvinyl)-4-acetylaniline and dimethyl diallyl ammonium chloride. We found that the particle size, morphology, functional groups, and fluorescence property of PTDNPs can be fine-tuned. Further, PTDNPs-0.10 were chosen as signal reporters to detect organophosphorus pesticides (OPs) with the aid of gold nanoparticles. Their sensing performance on OPs is superior to that using C-dot/quantum dot/rhodamine B as the signal reporter. This study not only provides new possibilities to fabricate novel AIE nanoparticles with exceptional properties, but also facilitates the AIE nanoparticle's application for target analyte biosensing.

Clinical utility in infants with suspected monogenic conditions through next-generation sequencing.

BACKGROUND: Rare diseases are complex disorders with huge variability in clinical manifestations. Decreasing cost of next-generation sequencing (NGS) tests in recent years made it affordable. We witnessed the diagnostic yield and clinical use of different NGS strategies on a myriad of monogenic disorders in a pediatric setting. METHODS: Next-generation sequencing tests are performed for 98 unrelated Chinese patients within their first year of life, who were admitted to Xin Hua Hospital, affiliated with Shanghai Jiao Tong University School of Medicine, during a 2-year period. RESULTS: Clinical indications for NGS tests included a range of medical concerns. The mean age was 4.4 ± 4.2 months of age for infants undergoing targeting specific (known) disease-causing genes (TRS) analysis, and 4.4 ± 4.3 months of age for whole-exome sequencing (WES) (p > 0.05). A molecular diagnosis is done in 72 infants (73.47%), which finds a relatively high yield with phenotypes of metabolism/homeostasis abnormality (HP: 0001939) (odds ratio, 1.83; 95% CI, 0.56-6.04; p = 0.32) and a significantly low yield with atypical symptoms (without a definite HPO term) (odds ratio, 0.08; 95% CI, 0.01-0.73; p = 0.03). TRS analysis provides molecular yields higher than WES (p = 0.01). Ninety-eight different mutations are discovered in 72 patients. Twenty-seven of them have not been reported previously. Nearly half (43.06%, 31/72) of the patients are found to carry 11 common disorders, mostly being inborn errors of metabolism (IEM) and neurogenetic disorders and all of them are observed through TRS analysis. Eight positive cases are identified through WES, and all of them are sporadic, of highly variable phenotypes and severity. There are 26 patients with negative findings in this study. CONCLUSION: This study provides evidence that NGS can yield high success rates in a tertiary pediatric setting, but suggests that the scope of known Mendelian conditions may be considerably broader than currently recognized.