Xin Yang

Newborn screening (NBS) is a critical component of the three-tiered prevention strategy for birth defects, reducing congenital disorder burden and improving long-term child health outcomes. Over the past 45 years, NBS in China has evolved into a nationwide quality-controlled network driven by policy support and technological advances. Currently, phenylketonuria and congenital hypothyroidism are included in universal NBS across the country, and several provinces have expanded to encompass congenital adrenal hyperplasia, glucose-6-phosphate dehydrogenase deficiency, and additional inherited metabolic disorders identified through tandem mass spectrometry. The application of next-generation sequencing and other technologies has further enhanced detection capacity and expanded detectable disease spectra. Meanwhile, the National Quality Management System for NBS (QMS-NBS) has realized the visualization and standardization of screening quality and performance. Despite these advances, challenges remain, including regional disparities, inadequate follow-up, and long-term management. This review summarizes the historical evolution and policy framework of NBS in China, outlines the development of screening institutions, the spectrum and incidence of screened disorders, advances in detection technologies, and the establishment of QMS-NBS. It also highlights future priorities: expanding screened conditions, strengthening follow-up and long-term care, promoting regional equity, and advancing novel technologies to improve child health and foster precision public health.

Silver–Russell syndrome (SRS) is most commonly caused by epigenetic alterations at 11p15.5 or maternal uniparental disomy of chromosome 7 [upd(7)mat], though other molecular mechanisms remain unclear. While microdeletions encompassing MEST have been associated with SRS-like phenotypes, no pathogenic intragenic MEST variants have been reported to date. We describe a 6-month-old male infant with clinical features suggestive of a SRS-like phenotype, including intrauterine and postnatal growth restriction, triangular facies, prominent forehead, and small extremities. Methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) revealed neither methylation abnormalities at 11p15.5, 7p13, or 7q32 nor copy number variations (CNVs) in these regions. Trio whole-exome sequencing (trio-WES) identified a paternally inherited splice-site variant (c.890 + 1G > A) in MEST. Given the paternal-specific expression of MEST, this variant resides on the functionally active allele. Based on in silico predictions and clinical correlation, this case identifies MEST as a plausible candidate gene for SRS and provides a rationale for further functional studies. Phenotypic variation exists across molecular subtypes, yet definitive genotype–phenotype correlations await larger, systematically ascertained cohorts.

Background: Pathogenic variants in ZNF292 cause intellectual disability type 64 (MIM#619188), characterized by intellectual impairment ranging from mild to severe, speech delay, and autism spectrum disorder. However, reports of ZNF292-related neurodevelopmental disorders remain scarce, and most published studies are based on multi-center cohorts. Methods: We performed whole-exome sequencing in eight unrelated individuals presenting with unexplained neurodevelopmental disorders, including global developmental delay and/or intellectual disability. Detailed clinical characterization, neuroimaging, and developmental assessments were conducted. Results: Seven de novo variants in ZNF292 were identified, including two nonsense and five frameshift variants, namely, c.4189C>T (p.Arg1397Ter), c.6343C>T (p.Arg2115Ter), c.1533del (p.Ile511Metfs*11), c.3094dup (p.Ser1032Phefs*18), c.3997_3998del (p.Thr1333Glnfs*8), c.6028_6031del (p.Ala2010Ter) and c.6160_6161del (p.Glu2054Lysfs*14). Among these, c.1533del (p.Ile511Metfs11), c.3094dup (p.Ser1032Phefs18) and c.3997_3998del (p.Thr1333Glnfs*8) are reported here for the first time. All variants were classified as pathogenic. All individuals exhibited global developmental delay, intellectual disability, and short stature. The majority presented with language impairment, motor delays, autism spectrum features, and dysmorphic facial features, while brain magnetic resonance imaging revealed nonspecific abnormalities such as ventriculomegaly. Conclusions: This study contributes additional cases to the expanding phenotypic and mutational spectrum of ZNF292-related neurodevelopmental disorder. Growth retardation was observed in all eight individuals, but given the limitations of a single-center referral cohort, this observation should be interpreted with caution and requires validation in larger studies.

Background: CLTC-related neurodevelopmental disorder is a rare condition primarily characterized by global developmental delay (GDD) and intellectual disability (ID). To date, approximately 41 cases involving CLTC gene alterations have been reported. We present the first individual with a complete deletion of the CLTC gene. Methods: The proband is a male from a non-consanguineous family, presenting with congenital nystagmus, hypotonia, GDD, and autism spectrum disorder (ASD). Chromosomal microarray analysis and trio exome sequencing were performed. A systematic review of previously reported CLTC variant cases was conducted to delineate the phenotypic spectrum. Results: A de novo 363-kb heterozygous deletion at 17q23.1 spanning the entire CLTC gene was identified. The systematic review confirmed GDD/ID as core features and revealed various ocular abnormalities in a subset of cases. These findings indicate that the clinical phenotype extends beyond neurodevelopment, with multi-system involvement. Conclusions: The phenotypic heterogeneity of CLTC-related disorders underscores the need for comprehensive physical examination to identify extra-neurological manifestations. Accurate diagnosis relies on integrating detailed clinical phenotyping with comprehensive genomic testing. Early, precise diagnosis facilitates multidisciplinary management, informed genetic counseling, and the establishment of long-term surveillance protocols.

Background and Objective: Asthma is a complex heterogeneous respiratory disease influenced by various factors such as genetics, immunity, and environment. Probiotics and related microbial preparations can be used in the prevention and treatment of asthma. This review aims to clarify the role and mechanism of microbial preparations in the treatment of asthma through respiratory administration, as well as the theoretical basis as delivery carriers. This may provide new insights for the prevention and treatment of asthma. Methods: This study employed the narrative review method and searched for articles published on PubMed between January 2007 and February 2026. The search terms included asthma, probiotics, airway microbiota, respiratory administration and nanoparticles. The inclusion criteria covered relevant original research, reviews, and guidelines, while editorials and articles lacking full text were excluded. Key Content and Findings: Alterations in airway microbiota are closely associated with the occurrence of asthma. Animal studies have demonstrated that oral intake of probiotics can effectively alleviate asthma symptoms, but their clinical application remains controversial. The main reasons include differences in study populations, asthma phenotypes, probiotic strains, dosages and treatment courses. The therapeutic effects and mechanisms of probiotic respiratory administration for asthma have been confirmed in animal experiments. Probiotics as delivery vehicles for respiratory administration in the treatment of asthma are theoretically feasible. Conclusions: Probiotics respiratory administration represents a potentially promising strategy to treat asthma. Probiotics as delivery vehicles can also be used to deliver anti-asthma drugs. However, current evidence is predominantly preclinical, and further studies are needed to optimize delivery, ensure safety and product standardization, and confirm clinical efficacy before routine clinical application.

Objective: To investigate the clinical characteristics, inheritance patterns, and genotype–phenotype correlations of DHX37 variants in 46,XY disorders of sex development (DSD). Methods: We retrospectively reviewed 108 patients with 46,XY karyotype who underwent DSD evaluation and trio-based whole-exome sequencing (trio-WES) at our center between January 2021 and December 2025. Six probands with DHX37 variants and no concurrent pathogenic or likely pathogenic variants in other known DSD-associated genes were analyzed in detail. Clinical presentations, endocrine profiles, imaging findings, and pedigree data were collected. Variant segregation was confirmed by Sanger sequencing; variants were assessed using in silico prediction, conservation analysis, and structural modeling, and were classified according to ACMG/AMP guidelines. Results: The six probands exhibited marked phenotypic heterogeneity, with manifestations ranging from complete gonadal dysgenesis to mild testicular underdevelopment with gynecomastia. Six heterozygous DHX37 missense variants were identified across distinct functional domains: one in RecA1 [c.1000C>T (p.Arg334Trp)], four in RecA2 [c.1379T>C (p.Val460Ala), c.1432G>A (p.Gly478Arg), c.1730A>G (p.Asp577Gly), and c.1954G>A (p.Val652Ile)], and one in the linker region proximal to the HA2 domain [c.2180C>T (p.Thr727Met)]. Of these, p.Arg334Trp is an established pathogenic variant; p.Gly478Arg has been reported previously, albeit in the same patient included in the present study; and the remaining four were novel. According to ACMG/AMP guidelines, p.Arg334Trp was classified as pathogenic, and the remaining five as variants of uncertain significance. Conclusions: This study provides additional case evidence supporting the pathogenicity of p.Arg334Trp and expands the DHX37 variant spectrum. Computational and structural analyses suggest that p.Gly478Arg may underlie the testicular regression syndrome phenotype of the corresponding proband and that the four novel variants may be involved in testicular development. However, these genotype–phenotype correlations remain speculative; larger cohorts and in vitro functional assays are warranted to confirm these associations.

Background: Tandem mass spectrometry (MS/MS) has been progressively integrated into newborn screening (NBS) in China over the past decades. However, variations exist in screening strategies, coverage and support systems across different regions. This study aims to investigate the current status of MS/MS-based NBS across China, providing insights into progress and future challenges. Methods: This retrospective investigation included 42 634 198 newborns screened at 267 NBS centres across 28 provinces in China between 2017 and 2021. These centres were divided into Eastern, Central and Western regions based on geographical location and economic development level. Data analysis focuses on screening rate, suspected positive rate, incidence and diagnostic efficiency of MS/MS-based NBS across these regions. Results: Over the 5-year study period, the nationwide MS/MS-based screening rate increased consistently from 36.93% in 2017 to 49.93% in 2021, with the prominent trend in the Central region. The suspected positive rates of amino acid metabolism disorders, organic acid metabolism disorders and fatty acid oxidation disorders showed a notable upward trend. In 2021, the nationwide incidences of amino acid metabolism disorders, organic acid metabolism disorders and fatty acid oxidation disorders were 15.34, 12.59 and 13.18 per 100 000 live births, respectively. Despite challenges, the diagnostic time for organic acid metabolism disorders in the Western region significantly improved, and similar ascending trends were observed for fatty acid oxidation disorders in most regions. Conclusion: Our findings highlight the remarkable progress of MS/MS in China’s NBS and its indispensable role as the primary method. Continued advancement will be key to improving health outcomes and safeguarding the well-being of newborns nationwide.

Background: The interplay between COVID‐19 pandemic and asthma in children is still unclear. We evaluated the impact of COVID‐19 pandemic on childhood asthma outcomes.Methods: The PeARL multinational cohort included 1,054 children with asthma and 505 non‐asthmatic children aged between 4 and 18 years from 25 pediatric departments, from 15 countries globally. We compared the frequency of acute respiratory and febrile presentations during the first wave of the COVID‐19 pandemic between groups and with data available from the previous year. In children with asthma, we also compared current and historical disease control.Results: During the pandemic, children with asthma experienced fewer upper respiratory tract infections, episodes of pyrexia, emergency visits, hospital admissions, asthma attacks, and hospitalizations due to asthma, in comparison with the preceding year. Sixty‐six percent of asthmatic children had improved asthma control while in 33% the improvement exceeded the minimal clinically important difference. Pre‐bronchodilatation FEV₁ and peak expiratory flow rate were improved during the pandemic. When compared to non‐asthmatic controls, children with asthma were not at increased risk of LRTIs, episodes of pyrexia, emergency visits, or hospitalizations during the pandemic. However, an increased risk of URTIs emerged.Conclusion: Childhood asthma outcomes, including control, were improved during the first wave of the COVID‐19 pandemic, probably because of reduced exposure to asthma triggers and increased treatment adherence. The decreased frequency of acute episodes does not support the notion that childhood asthma may be a risk factor for COVID‐19. Furthermore, the potential for improving childhood asthma outcomes through environmental control becomes apparent.