OBJECTIVES: To determine the diagnostic and clinical utility of trio-rapid genome sequencing in critically ill infants. DESIGN: In this prospective study, samples from critically ill infants were analyzed using both proband-only clinical exome sequencing and trio-rapid genome sequencing (proband and biological parents). The study occurred between April 2019 and December 2019. SETTING: Thirteen member hospitals of the China Neonatal Genomes Project spanning 10 provinces were involved. PARTICIPANTS: Critically ill infants (n = 202), from birth up until 13 months of life were enrolled based on eligibility criteria (e.g., CNS anomaly, complex congenital heart disease, evidence of metabolic disease, recurrent severe infection, suspected immune deficiency, and multiple malformations). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of the 202 participants, neuromuscular (45%), respiratory (22%), and immunologic/infectious (18%) were the most commonly observed phenotypes. The diagnostic yield of trio-rapid genome sequencing was higher than that of proband-only clinical exome sequencing (36.6% [95% CI, 30.1–43.7%] vs 20.3% [95% CI, 15.1–26.6%], respectively; p = 0.0004), and the average turnaround time for trio-rapid genome sequencing (median: 7 d) was faster than that of proband-only clinical exome sequencing (median: 20 d) (p < 2.2 × 10–16). The metagenomic analysis identified pathogenic or likely pathogenic microbes in six infants with symptoms of sepsis, and these results guided the antibiotic treatment strategy. Sixteen infants (21.6%) experienced a change in clinical management following trio-rapid genome sequencing diagnosis, and 24 infants (32.4%) were referred to a new subspecialist. CONCLUSIONS: Trio-rapid genome sequencing provided higher diagnostic yield in a shorter period of time in this cohort of critically ill infants compared with proband-only clinical exome sequencing. Precise and fast molecular diagnosis can alter medical management and positively impact patient outcomes.

Objective We describe the clinical and genetic features, drug use and neuropsychiatric disorders of infants diagnosed with tuberous sclerosis complex (TSC) within 3 months of age at a neonatal intensive care unit (NICU) to better understand the different outcomes from early screening. Methods In this retrospective study, we consisted of 42 infants with a definitive TSC diagnosis by genetic criteria (TSC1 = 8, TSC2 = 34). The different phenotypes and outcomes between patients with TSC1 and TSC2 mutations were analyzed. Results The most common initial presenting features of TSC were cortical tubers on magnetic resonance imaging (50%), hypomelanotic macules on skin (47.61%) and spasm (42.85%), when they were diagnosed. Following disease progression to time of follow-up 1 year later, we found that the rate of epilepsy increased from 42.85% to 75.61% and that of cardiac rhabdomyoma increased from 28.57% to 43.9%. The median age at first presentation was 7.84 ± 1.88 months. We also found that 54.83% of patients on medication were seizure free for over 1 year, and that 43.9% of patients have intellectual disability. In total, 42 variants of TSC were detected, including 12 novel variants. We found no evidence of an association between different clinical features and their outcomes among patients with different gene mutations. Conclusion Early diagnosis of TSC in NICU opens a window of opportunity for early, more effective treatment of epilepsy as well as reduces the risk of neurological conditions.

Background: A low-phenylalanine (Phe) diet affects the metabolism and diversity of gut microbial communities in children with phenylketonuria (PKU). Our study examined gut microbiota characteristics and metabolic pathways, and their correlations with clinical phenotypes in a high-incidence population. Methods:We assessed clinical phenotypes and gut microbiota by 16S ribosomal RNA (rRNA) sequencing, and performed a correlation analysis between phenotype and gut microbiota in a PKU group (n=11) and a healthy group (n=11). Results:The PKU group had significantly lower microbiota diversity than the healthy group (P shannon =0.014).Phylum-level composition differed significantly between the PKU and healthy groups (Firmicutes: 44.3% vs.

Background: Neonatal hyperphenylalaninemia (HPA) screening did not begin until 2009 in the Uygur population because of poor medical and economic conditions. This study intended to investigate HPA incidence rate and characterize mutation spectrum of phenylalanine hydroxylase (PAH) gene within the Uygur population.Methods: Cross-sectional data of National Direct Reporting System database from 2009 to 2016 were used to calculate incidence rate. All HPA positive newborns were diagnosed and confirmed by Sanger sequencing.A low Phe diet was implemented.Results: A total of 580,608 Uygur neonates were screened, 111 were diagnosed with HPA with an incidence rate of 1:5,230, 58 different mutations in PAH gene were detected. Eight novel variants were found, including two nonsense mutations (L11*, L197*), two splicing mutations (IVS12-2A > C, IVS13-1G > A), one frameshift mutation (K115 > Hfs) and three missense mutations (E368K, E370G, D435V), distributing in twenty patients. A104D was the most frequent mutation in this study, and the other hot spot of R413P was found in 4 patients in a same Uygur village with a carrier rate of 1:2.1.Conclusions: This is the first study to investigate HPA incidence rate in the Uygur population. Our study highlights regional differences in PAH genotypes and mutation rates.

Motivation is one of the important factors that influence English learning achievement. That's true of the students in the Senior Middle School. In order to improve the students' English performance, a research by means of a questionnaire and an interview is done in a key Senior School on the motivation in learning English in order to improve the English teaching. The results showed that the motivation has a close relationship with the students' performance. But the different strength in motivation will lead to different learning efficiency. So to help the students to maintain a proper strength in English learning motivation is very necessary for the teachers in the daily teaching procedure. Finally, some suggestions are available to the teachers.