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To examine the overall genomic copy-number variant (CNV) landscape of Chinese pediatric patients with developmental disorders. De-identified chromosomal microarray (CMA) data from 10,026 pediatric patients with developmental disorders were collected for re-evaluating the pathogenic CNV (pCNV) yields of different medical conditions and for comparing the frequency and phenotypic variability of genomic disorders between the Chinese and Western patient populations. The overall yield of pCNVs in the Chinese pediatric patient cohort was 21.37%, with variable yields for different disorders. Yields of pCNVs were positively associated with phenotypic complexity and intellectual disability/developmental delay (ID/DD) comorbidity for most disorders. The genomic burden and pCNV yield in neurodevelopmental disorders supported a female protective effect. However, the stratification analysis revealed that it was seen only in nonsyndromic ID/DD, not in nonsyndromic autism spectrum disorders or seizure. Furthermore, 15 known genomic disorders showed significantly different frequencies in Chinese and Western patient cohorts, and profiles of referred clinical features for 15 known genomic disorders were also significantly different in the two cohorts. We defined the pCNV yields and profiles of the Chinese pediatric patients with different medical conditions and uncovered differences in the frequency and phenotypic diversity of genomic disorders between Chinese and Western patients.

The gene encodes a G-protein coupled receptor that plays a pivotal role in sexual differentiation in males, ovarian development in females and in fertility via its interaction with luteinizing hormone and chorionic gonadotropin. Inactive variants of the gene cause Leydig cell hypoplasia (LCH), which is a rare disease and one of the causes of disorder of sexual differentiation (DSD) in males. The aim of this work was to clarify the clinical and molecular characteristics of a 2.75 year old patient with type 1 LCH. Whole exome sequencing was performed for the patient family and variants in the gene were validated by Sanger sequencing. Pathogenicity of the missense variant was evaluated by multiple tools. Our Chinese patient, who exhibited DSD, had female external genitalia (normal labia majora and minora, external opening of urethra under the clitoris and blind-ended vagina) and bilateral testis tissues in the inguinal region. Genetic sequencing revealed compound heterozygous variants in the gene in the patient, including a novel missense variant in exon 4 (c.349G>A, p.Gly117Arg) and a novel nonsense variant in exon 10 (c.878C>A, p.Ser293*). The missense variant is in the first leucine-rich repeat domain of the protein, which is predicted to affect ligand recognition and binding affinity and thus protein function. The patient is molecularly and clinically diagnosed with type 1 LCH, which is caused by novel, compound heterozygous variants of the gene. We believe this report will serve to expand the genotypic spectrum of variants.

Background Growth chart is a valuable clinical tool to monitor the growth and nutritional status of children. A growth chart widely used in China is based on the merged data sets of national surveys in 2005. We aimed to establish an up-to-date, complete growth curve for urban Chinese children and adolescents with a full range of ages. Methods Using data collected in a large-scale, cross-sectional study (Prevalence and Risk factors for Obesity and Diabetes in Youth (PRODY), 2017–2019), we analyzed 201,098 urban children aged 3 to 18 years from 11 provinces, autonomous regions, and municipalities that are geographically representative of China. All participants underwent physical examinations. Sex-specific percentiles of height-for-age and weight-for-age were constructed by Generalized Additive Models for Location Scale and Shape (GAMLSS) model. We also compared the median values of height-for-age or weight-for-age between our growth chart and the established growth reference using Welch-Satterthwaite T-Test. Results Consistent with the established growth reference, we observed that the P 50 percentile of height-for-age reached plateaus at the age of 15 years (172 cm) and 14 years (160 cm) for boys and girls, respectively. In addition, boys aged 10 ~ 14 years and girls aged 10 ~ 12 years exhibited the most dramatic weight difference compared to those of other age groups (19.5 kg and 10.3 kg, respectively). However, our growth chart had higher median values of weight-for-age and height-for-age than the established growth reference with mean increases in weight-for-age of 1.36 kg and 1.17 kg for boys and girls, respectively, and in height-for-age of 2.9 cm and 2.6 cm for boys and girls, respectively. Conclusions Our updated growth chart can serve as a reliable reference to assess the growth and nutritional status in urban Chinese children throughout the entire childhood.

The increasing incidence of precocious puberty is a major health challenge for Chinese children, while related risk factors remain less well explored. Exposure to ambient fine particulate matter (PM2.5) is a leading environmental hazard in China. Although certain components of PM2.5 have been reported to be endocrine disruptors for sex hormones, population-based evidence is still lacking on the association between PM2.5 exposure and precocious puberty in China. Based on a cross-sectional survey covering 30 cities in 2017 to 2019, this study was designed to explore the association between long-term exposure to PM2.5 and its 5 major components with precocious puberty in China and to check the potential modifying effects of family-related and personal factors. We included 34,105 children aged 6 to 9 years. We collected the 5-year average concentrations of PM2.5 and its 5 major components (sulfate, nitrate, ammonium, organic matter, and black carbon) in the area (at a spatial resolution of 0.1° × 0.1°) where each school was located. We used mixed effect logistic regression to estimate the effect sizes of the total mass of PM2.5 and each of its components on precocious puberty, and we examined the modifying effects of family-related and personal factors using an additional interactive term. A weighted quantile sum (WQS) regression model was applied to identify the weights of each component in explaining the effect size of the total mass of PM2.5. We found that the odds ratio (OR) for precocious puberty per IQR increase in the concentration of total PM2.5 mass was 1.27 (95% CI 0.92-1.75) for the whole population, 2.12 (95% CI 1.27-3.55) for girls, and 0.90 (95% CI 0.62-1.30) for boys. Similarly, the effect sizes of the 5 major components were all substantial for girls but minimal for boys. Results of the WQS analysis showed that organic matter could explain the highest proportion of the effect of PM2.5, with the weight of its contribution being 0.71. Modification effects of family income and dietary habits were only observed in certain population subgroups. Long-term exposure to total PM2.5 mass was significantly associated with precocious puberty in girls, with organic matter identified as the major effect contributor. The results add evidence on the detrimental effects of PM2.5 on children's development and growth.

Lepus tibetanus pamirensis distributes only in the Pamir Plateau under a harsh environment with high attitude, cold and dry climates. The complete mitochondrial genome of the hare was determined (accession number MN539746) in a total length of 16,753 bp. The overall base composition of L. t. pamirensis mitogenome is 31.6% for A, 25.7% for C, 13.3% for G and 29.5% for T. It has the common characteristic with other mammals in regard to genome structure and gene arrangement. Based on published complete mitogenome sequences of lagomorphs, the phylogenetic tree suggested that L. t. pamirensis is closely related to L. yarkandensis and has far relationship with L. capensis. Our results would provide useful information for further study on conservation genetics and evolution of this hare species.

Pierson syndrome (OMIM 609049) is a rare autosomal recessive disorder characterized by congenital nephrotic syndrome and complex ocular abnormalities. Severe renal symptoms had be associated with truncating mutations. Few Chinese patients from diverse ethnic background had been evaluated and reported with this syndrome. Here we report the first Uyghur patient with typical Pierson syndrome phenotypes and a novel pathogenic homozygous variant in gene. A thirty-nine-day old Uyghur girl was born to consanguineous parents, the girl presented with general edema, severe hypotonia and bilateral microcoria. Laboratory tests revealed severe proteinuria, microscopic haematuria, hypoalbuminaemia. By the age of 74 days, she died of renal failure and respiratory infection. We detected on mutations of gene by the sanger sequencing. Sanger sequencing detected a homozygous 2-bp deletion (c.2044_2045insTT/p.Cys682Phefs 13) in the exon 16 of gene. Both parents are heterozygous carriers. We reported the first Uyghur case of gene homozygous mutation leading to severe phenotype Pierson syndrome. The clinical presentation of the patient and the novel pathogenic variant detected in this patient added to the overall knowledge of this rare condition.

Glycogen-storage disease type II (GSDII) is an autosomal recessive disorder caused by a deficiency of acid α-glucosidase (GAA). The residual GAA activity is largely related to the severity of the clinical course. Most patients with infantile-onset GSDII do not show any enzyme activity, whereas patients with the late-onset forms of GSDII show various degrees of GAA activity. We performed a molecular genetic study on a Japanese boy with childhood-onset GSDII. The patient was a compound heterozygote for a newly discovered splice-site c.546G>T mutation and a recurrent missense p.R600C mutation, which usually causes the fatal infantile form in a homozygous state. The c.546G>T mutation, which did not alter the amino-acid sequence, was positioned at the last base of exon 2. cDNA-sequencing analysis revealed that c.546G>T was a leaky splice mutation, leading to the production of a normally spliced transcript, which was responsible for the low-level (approximately 10%) expression of the active enzyme in the patient's fibroblasts.

Abstract Context Age of pubertal onset has been decreasing in many countries but there have been no data on pubertal development in Chinese children over the last decade. Objective The primary objective of the study was to evaluate the current status of sexual maturation in Chinese children and adolescents. Secondary objectives were to examine socioeconomic, lifestyle, and auxological associations with pubertal onset. Methods In this national, cross-sectional, community-based health survey, a multistage, stratified cluster random sampling method was used to select a nationally representative sample, consisting of 231 575 children and adolescents (123 232 boys and 108 343 girls) between 2017 and 2019. Growth parameters and pubertal staging were assessed by physical examination. Results Compared to 10 years previously, the median age of Tanner 2 breast development and menarche were similar at 9.65 years and 12.39 years respectively. However, male puberty occurred earlier with a median age of testicular volume ≥4 mL of 10.65 years. Pubertal onset did occur earlier at the extremes, with 3.3% of the girls with breast development at 6.5-6.99 years old, increasing to 5.8% by 7.5-7.99 years old. Early pubertal onset was also noted in boys, with a testicular volume ≥ 4 mL noted in 1.5% at 7.5-7.99 years, increasing to 3.5% at 8.5-8.99 years old. Obesity and overweight increased risk of developing earlier puberty relative to normal weight in both boys and girls. Conclusion Over the past decade, pubertal development is occurring earlier in Chinese children. While the cause is multifactorial, overweight and obesity are associated with earlier puberty onset. The currently used normative pubertal data of precocious puberty may not be applicable to diagnose precocious puberty.

Abstract Context Aggrecan, encoded by the ACAN gene, is the main proteoglycan component in the extracellular cartilage matrix. Heterozygous mutations in ACAN have been reported to cause idiopathic short stature. However, the prevalence of ACAN pathogenic variants in Chinese short stature patients and clinical phenotypes remain to be evaluated. Objective We sought to determine the prevalence of ACAN pathogenic variants among Chinese short stature children and characterize the phenotypic spectrum and their responses to growth hormone therapies. Patients and Methods Over 1000 unrelated short stature patients ascertained across China were genetically evaluated by next-generation sequencing–based test. Result We identified 10 novel likely pathogenic variants and 2 recurrent pathogenic variants in this cohort. None of ACAN mutation carriers exhibited significant dysmorphic features or skeletal abnormities. The prevalence of ACAN defect is estimated to be 1.2% in the whole cohort; it increased to 14.3% among those with advanced bone age and to 35.7% among those with both advanced bone age and family history of short stature. Nonetheless, 5 of 11 ACAN mutation carries had no advanced bone age. Two individuals received growth hormone therapy with variable levels of height SD score improvement. Conclusion Our data suggest that ACAN mutation is 1 of the common causes of Chinese pediatric short stature. Although it has a higher detection rate among short stature patients with advanced bone age and family history, part of affected probands presented with delayed bone age in Chinese short stature population. The growth hormone treatment was moderately effective for both individuals.

Obesity is a public health challenge in China, but the geographical profiles of overweight and obesity among Chinese children are limited. To examine regional disparities in the prevalence of obesity among the heterogeneous population of Chinese children and adolescents to provide a more accurate profile of obesity among children in China. The Prevalence and Risk Factors for Obesity and Diabetes in Youth (PRODY) study was a cross-sectional survey study conducted from January 1, 2017, to December 31, 2019, among 201 098 children aged 3 to 18 years from 11 provinces, autonomous regions, and municipalities that produced a sample of Chinese children with a full range of ages and wide geographical coverage using a multistage, stratified, cluster-sampling design. Five regions geographically representative of China (northern, eastern, southern, western, and central). The body weights and heights of all participants were measured. Multilevel, multinomial logistic regression models were used to estimate the prevalence of overweight and obesity. Among 201 098 healthy children (105 875 boys [52.6%]; mean [SD] age, 9.8 [3.8] years) from eastern, southern, northern, central, and western China, the highest obesity prevalence was estimated for children aged 8 to 13 years in northern China (from 18.8% [95% CI, 16.2%-21.7%] to 23.6% [95% CI, 20.5%-26.9%]) and for boys aged 3 to 6 years in western China (from 18.1% [95% CI, 10.4%-29.4%] to 28.6% [95% CI, 14.3%-49.0%]). Boys had a higher prevalence than girls of obesity only in eastern and northern China, with a mean difference in prevalence of 4.6% (95% CI, 3.8%-5.4%) and 7.6% (95% CI, 6.5%-8.6%), respectively. In this survey study, substantial geographic disparities in the prevalence of obesity and overweight were found among the heterogeneous population of Chinese children. The results suggest that special attention should be paid to vulnerable children and that regionally adapted interventions are needed to efficiently mitigate obesity in children.