OBJECTIVE: To analyze the metabolic profile and genetic variants for newborns with primary carnitine deficiency (PCD) from Guangxi, China. METHODS: From January 2014 to December 2019, 400 575 newborns from the jurisdiction of Guangxi Zhuang Autonomous Region Newborn Screening Center were subjected to tandem mass spectrometry (MS/MS) analysis. Newborns with positive results for PCD and their mothers were recalled for retesting. Those who were still positive were subjected to sequencing of the SLC22A5 gene. RESULTS: Twenty-two newborns and 9 mothers were diagnosed with PCD, which gave a prevalence rate of 1/18 208. Sequencing of 18 newborns and 4 mothers have identified 14 types of SLC22A5 gene variants, with the common ones including c.51C>G (10/44, 22.7%), c.1195C>T (9/44, 20.5%) and c.1400C>G (7/44, 15.9%), The c.517delC(p.L173Cfs*3) and c.1031C>T(p.T344I) were unreported previously and predicted to be pathogenic (PVS1+PM2_supporting+PM3+PP4) and likely pathogenic (PM1+PM2_supporting+PM3+PP3+PP4) based on the American College of Medical Genetics and Genomics standards and guidelines. CONCLUSION c.51C>G, c.1195C>T and c.1400C>G are the most common variants underlying PCD in Guangxi.
Cardiomyopathies ; Carnitine/deficiency* ; China ; Humans ; Hyperammonemia ; Infant, Newborn ; Metabolome ; Muscular Diseases ; Mutation ; Solute Carrier Family 22 Member 5/genetics* ; Tandem Mass Spectrometry

Objective:To investigate the impact of different feedback methods on the training effects of laparoscopic simulation training learners in two-week training course.Methods:A total of 98 trainees receiving simulation laparoscopic training from August 2017 to April 2018 in The First Affiliated Hospital of Xinjiang Medical University were randomized into three groups, including Group 1 ( n=32), watching video tutorials only; Group 2 ( n=33), watching video tutorials and receiving immediate feedback; Group 3 ( n=33) watching video tutorials and receiving conclusive feedback. All the trainees received assessment before and after the training. The differences of assessment scores and operation time before and after the training were compared among the three groups. Chi-square test and t test were conducted by STATA 11.0. Results:The assessment scores of the three groups were significantly improved after the training than before ( P<0.05), and the operation time of the three groups were significantly shorter than before ( P<0.05). The assessment scores and operation time of Group 3 after the training were significantly better than the other two groups ( P<0.05), and the assessment scores of Group 3 were higher than those of the other two groups ( P<0.05), but there was no significant difference between the other two groups ( P >0.05). There were significant differences in training duration and repetition times among the three groups ( P<0.05). The training duration and repetition times of Group 3 were significantly less than those of the other two groups ( P<0.05). Conclusion:Compared with the other two groups, conclusive feedback can greatly accelerate learning and improve training efficiency in laparoscopic simulation training.

Objective:To analyze the trends of overweight and obesity prevalence in Chinese children, aged from 6 to 15 years old among 4 provinces and cities from 2009 to 2019.Methods:Reviewed the national multi-center epidemiological survey data of children from the National Key Technology R&D Program of China during the Eleventh Five-Year Plan (2009 to 2010) and the National Key Research and Development Program of China during the Thirteenth Five-Year Plan (2017 to 2019). The participants′ data were selected from four provinces,municipalities and autonomous region,including Beijing, Tianjin (Northern region), Zhejiang (Eastern region), and Guangxi (Southern region). Totally 14 597 pairs of 6-15 year-old children were surveyed. According to the body mass index (BMI) and standard deviation score (SDS) of children among different genders, ages, and regions, t test or chi-square test was used to evaluate the changes in overweight and obesity over a 10-year span. Results:Totally 7 721 pairs of boys and 6 876 pairs of girls were collectted in this study, whose mean age was (10.7±2.5) years. In the past 10 years, the overall BMISDS were 0.39±1.24 and 0.36±1.31 and the overall obesity rate were 11.8% ( n=1 773) anel 12.5% ( n=1 813) of children in the 4 administrative regions did not have statistically significant differences (all P>0.05). However, the overall overweight rate rose from 17.1% ( n=2 496) to 19.1% ( n=2 781) (χ2=18.657, P<0.01), and the average annual growth rate was 0.20%. The BMISDS in the Eastern region increased from 0.10±1.07 to 0.19±1.22 ( t=-4.095, P<0.01), and the overweight rate and obesity rate increased by 3.8% ( n=202) and 3.1% ( n=169) respectively (both P<0.01); the BMISDS in the Northern region and the obesity rate did not have statistically significant differences(all P>0.05), but the overweight rate rose from 20.5% ( n=1 233) to 22.8% ( n=1 365) significantly (χ2=7.431, P<0.01); BMISDS in the Southern region was significantly decreased from 0.30±1.19 to 0.09±1.25 ( t=1.426, P<0.01), and the rate of obesity decreased from 9.8% ( n=315) to7.9% ( n=256) (χ2=6.46, P<0.05), the overweight rate was not stafistically significant ( P=0.10), respectively. The obesity rate of boys had risen from 16.4% ( n=1 265) to 18.2% (1 407) (χ2=8.997, P<0.01) in the past 10 years, and the overweight rate had risen from 18.0% ( n=1 393) to 20.5% ( n=1 579) (χ2=14.26, P<0.01). The overweight+obesity rate rose from 34.4% ( n=2 658) to 38.7% ( n=2 986) (χ2=29.859, P<0.01), and the weight problem in the age group of 8 to 11 years was particularly severe (all P<0.01). The obesity rate of girls dropped from 6.8% ( n=468) to 5.9% ( n=406) (χ2=4.546, P<0.05), the overweight rate rose from 16.0% ( n=1 103) to 17.5% ( n=1 202) (χ2=5.006, P<0.05), and the overall overweight+obesity rate rose from 22.8% ( n=1 571) to 23.4% ( n=1 608) (χ2=0.53, P>0.05). Conclusions:The growth rate of obesity among children in China had slowed down from 2009 to 2019, but the overweight rate was still on the rise. The overall base of overweight and obesity population continued to expand. The weight problem of peri-adolescent boys was particularly prominent. The current status of obesity epidemics in different regions, ages, and genders are significantly different and had their own characteristics. It is necessary to establish a personalized prevention and control strategy.

Objective:To investigate the status of height and weight of 3-18-year-old children and adolescents in urban China, and to provide a basis for establishing puberty phase specific curves for age-specific height and age-specific weight.Methods:A cross-sectional survey of 218 185 children and adolescents aged 3-18 years in urban China was conducted by using the method of stratified random cluster sampling from January 2017 to December 2019. The sampling areas included 12 provinces municipalities in China and autonomous regions in total. Data were collected on weight, height, waist circumference, hip circumference and secondary sexual characteristics. The generalized additive model for location, scale, and shape (GAMLSS) was employed to establish percentile reference values and growth curves of height and weight for boys and girls aged 3-18 years. Wilcoxon rank sum test was applied to compare the P 50 value of height and weight between children of each Tanner stage and children of the same age ignoring the different puberty phase. Results:The 3rd, 50th, and 97th percentile curves for height and weight for age were developed for boys and girls aged 3-18 years. The 3rd, 50th, and 97th percentile curves for age-specific height and age-specific weight for each puberty phase were developed for boys and girls. Compared with all children ignoring the different puberty phase, boys aged 9 and over and girls aged 7 and over who are at Tanner stage 1 showed shorter height and lighter weight than those of the same age group (all P<0.01), the difference ranges of height at P 50 are -4.0 to -0.6 cm for boys, and -4.4 to 0.5 cm for girls; the difference ranges of weight are -4.8 to 0.4 kg for boys, and -4.0 to -0.3 kg for girls; children at Tanner stage 2 & 3 initially were taller and heavier than those of the same age group; and later grew shorter and lighter than those of the same age group, the two sets of curves cross over; boys aged 16 and under and girl aged under 14 who are at Tanner stage 4 were taller and heavier than those of the same age group (all P<0.01), the difference ranges of height at P 50 are 0.2 to 10.0 cm for boys, and 0.2 to 9.4 cm for girls; the difference ranges of weight at P 50 are 0.7 to 10.9 kg for boys, and 1.0 to 11.2 kg for girls, and the differences showed narrowing trend with age. Conclusion:The puberty phase specific growth curves of age-specific height and age-specific weight for boys and girls aged 3-18 years are established, it is useful for clinical work to evaluate physical development of children at different puberty phases.

Objective To investigate the characteristics of the phenylalanine hydroxylase( PAH)gene muta﹣tions in patients With phenylketonuria(PKU)in Guangxi region,in order to provide clinical data for genetic counseling and prenatal gene diagnosis. Methods Thirty－seven children diagnosed as PKU in the Maternal and Children＇s Hos﹣pital of Guangxi Zhuang Autonomous Region Were enrolled in the study betWeen January 2009 and December 2017. Ve﹣nous blood Was collected and the PAH gene sequence Was determined by Sanger sequencing after amplification With the polymerase chain reaction technique. The neW gene mutations Were defined based on the national and international literature revieW and databases. MeanWhile,100 healthy individuals Were selected as the control group for gene sequen﹣cing to confirm Whether the mutation Was a neW one. Results Thirty－seven cases of PKU Were detected for 68 muta﹣tions,With the detection rate being 91. 89%(68／74). Six mutations Were identified in exon 7,Which accounted for 31. 08% of all,exon 12(18. 92%),exon 8(10. 81%)and exon 6(10. 81%)folloWed. A total of 25 different muta﹣tions Were identified Which including 14 missense mutations(56. 00%),7 nonsense mutations(28. 00%),3 splicing junction mutations(12. 00%),and 1 deletion mutation(4. 00%). The most common mutations included c. 1223G＞A (p. R408Q),c. 728G＞A(p. R243Q)and c. 721C＞T( p. R241C),accounting for 14. 86%,13. 51%,and 10. 81%, respectively. After querying international databases,including PAH mutation database and Human Gene Mutation Data﹣base and forecasting softWare,three kinds of mutations c. 314C＞ T(p. T105I),c. 583A＞ G(p. K195E),c . 851G＞A(p. C284Y)Were verified as novel PAH gene mutations. Conclusions The mutation spectrum of the PAH gene in Guangxi has been identified. And 3 kinds of mutations have been identified. This may accumulate valuable information for gene diagnosis and prenatal diagnosis of PKU in Guangxi region.

Objective: To investigate the clinical, biochemical and genetic features of four carnitine-acylcarnitine translocase deficiency cases. Methods: Four cases diagnosed with carnitine-acylcarnitine translocase deficiency from Guangxi Maternal and Child Health Hospital were studied. DNA was extracted from dry blood filter for gene analysis. SLC25A20 gene analysis was performed in 1 case and the whole exon sequence analysis was performed in 3 cases. Results: Retrospective study on unrelated carnitine-acylcarnitine translocase deficiency patients, the age of onset was 1-28 d, the age of death were 1.5-30 d, main clinical features were hypoglycemia (4 cases), arrhythmia (2 cases), sudden death (2 cases). Biochemical test showed hypoglycemia (1.2-2.0 mmol/L) , elevated creatine kinase (955-8 361 U/L) and creatine kinase isozyme(199-360 U/L), normal or decreased free carnitine level (3.70-27.07 μmol/L) , elevated long-chain acylcarnitine (palmityl carnitine 1.85-14.84 μmol/L). The gene tests showed that all 4 cases carried SLC25A20 gene c.199-10T> G homozygous mutation, inherited from their parents. By analyzing the haplotype, we found that the mutation loci of C. 199-10T> G were all in the same haplotype. Conclusion The c.199-10T> G mutation is an important molecular cause of carnitine-acylcarnitine translocase deficiency, which has relatively high frequency in Guangxi population, and is related to the founder effect.

Objective To compare cortical bone screwing and Endobutton plating for the treatment of ankle joint fracture complicated with injury to the distal tibiofibular syndesmosis. Methods Fifty-eight pa-tients with ankle joint fracture and injury to the distal tibiofibular syndesmosis were treated at Department of Orthopedic Surgery, The Affiliated Hospital to Guangdong Medical University from January 2014 to June 2016. Half of them were treated by conventional cortical bone screwing. They were 16 males and 13 females with an average age of 43.2 ± 4.1 years. The other half were treated by Endobutton plating. They were 15 males and 14 females with an average age of 44.1 ± 3.9 years. The 2 groups were compared in terms of intraoperative bleed-ing, operation time, tibiofibular clear space ( TBCS ) , tibiofibular overlap ( TBOL ) , the American Orthopedic Foot Ankle Society (AOFAS) ankle-hindfoot scale and complications. Results The cortical bone screwing group needed significantly shorter operation time (63.4 ± 5.4 min) than the plating group (89.6 ± 6.2 min) ( P ＜0.05) . There were no significant differences between the 2 groups in intraoperative bleeding ( 68.9 ± 6.3 mL versus 67.4 ± 6.4 mL ) , TBCS ( 4.6 ± 0.3 mm versus 4.7 ± 0.3 mm) , TBOL ( 7.5 ± 0.4 mm versus 7.4 ± 0.4 mm ) , good to excellent rate by AOFAS score ( 72.4% versus 75.9%) , or rate of complications ( 6.9% versus 10.3%) ( P ＞ 0.05 ). Conclusion Since cortical bone screwing and Endobutton plating show no signifi-cant difference for the treatment of ankle joint fracture complicated with distal tibiofibular syndesmosis injury, a proper surgical procedure should be decided according to the specific conditions of the patient.

OBJECTIVETo explore the value of single nucleotide polymorphism array (SNP-array) for the analysis of pediatric patients with growth retardation.

METHODSOne hundred eighty one children with growth retardation were enrolled. DNA was extracted from peripheral samples from the patients, and whole genome copy number variations (CNVs) were detected using Illumina Human Cyto SNP-12. All identified CNVs were further analyzed with reference to databases including ClinGen, ClinVar, DECIPHER, OMIM and DGV as well as comprehensive review of literature from PubMed to determine their pathogenicity.

RESULTSForty seven patients (26%) with abnormal CNVs were detected, which included 12 known microdeletions/microduplications syndrome (26%), 10 pathogenic non-syndromic CNVs (21%), 3 numerical chromosome aberrations (6%), 3 unbalanced translocations (6%), 4 pathogenic mosaicisms (9%) and 15 cases with unknown clinical significance (32%). After excluding obvious numerical and/or structural chromosomal abnormalities, this study has detected 15 pathogenic microdeletions/microduplications sized 5 Mb or less, which may be missed by routine chromosomal karyotyping. In addition, there were 3 cases with loss of heterozygoisty (LOH) containing known or predicted imprinting genes as well as 2 cases with suspected parental consanguinity.

CONCLUSIONSNP-array technology is a powerful tool for the genetic diagnosis of children with growth disorders with advantages of high resolution and improved accuracy.

Adolescent ; Child ; Child, Preschool ; Chromosome Aberrations ; DNA Copy Number Variations ; Developmental Disabilities ; diagnosis ; genetics ; Female ; Humans ; Infant ; Karyotyping ; Male ; Oligonucleotide Array Sequence Analysis ; methods ; Polymorphism, Single Nucleotide

Objective To investigate the genetic basis of patients with intellectual disability,and to assess the application of single nucleotide polymorphisms (SNP)-array in the molecular diagnosis of intellectual disability.Methods Sixty-four patients with intellectual disability who were identified in Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region from January 2013 to June of 2015 were enrolled.Genomic DNA was extracted from peripheral blood and was analyzed with Illumina Humancyto SNP-12 300K gene array chip.All identified copy number variants (CNVs) were analyzed with references from databases such as ClinVar,DECIPHER,OMIM and DGV(Database of Genomic Variants),as well as comprehensive literature review from PubMed database to determine the pathogenicity of CNVs.Results Sixteen cases of the above 64 patients were found to have CNVs with genomic alterations,including 6 cases microdeletions/microduplications associated with known syndromes,3 cases microdeletions and microduplications with clear clinical relevance (non-syndrome),1 case numerical chromosome aberration,1 case unbalanced translocation and 5 cases CNVs of unknown clinical significance.The detection rate was 25% (16/64 cases).Among these 16 abnormalities,6 cases of them could not be detected by using karyotyping analysis because their sizes were less than 5 Mb,and the smallest detected missing fragment was 0.53 Mb.Conclusion SNP-array gene chip technique with the advantages of higher efficiency,high-resolution and good accuracy,which can be applied to the genetic diagnosis of intellectual disability.

Objective Design short stature panel with gene curration strategy.Methods The gene curation process was introduced in detail.The strength of a gene-disease relationship was evaluated based on publicly available genetic and experimental evidence.This process in short stature panel design and its effect on gene selection was further demonstrated.Results After gene curation, the number of gene in list was effectively decreased from 1 276 to 705.The panel sequencing reached a diagnosis rate of 19.7% among a cohort of 371 nation-wide ascertained short stature patients.The gene curation process reduced the risk of false positive findings and decreased diagnostic cost and working hours without affecting the diagnosis rate.Conclusion Gene curation is an important step for NGS-based test and should be widely exercised.