Objective:To explore the incidence, clinical features, genetic variant characteristics and prognosis of Glutaric acidemia type I (GA1) among neonates from Henan Province.Methods:A total of 814 625 neonates undergoing screening for inherited metabolic diseases by tandem mass spectrometry (MS/MS) at the Third Affiliated Hospital of Zhengzhou University from January 2016 to December 2022 were selected as the study subjects. A retrospective method was adopted to collect the clinical data of the patients. Whole exome sequencing was carried out to detect GCDH gene variants in individuals with positive results by GA1 newborn screening, and Sanger sequencing was used to verify the candidate variants. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the pathogenicity of candidate variants was rated. This study was approved by the Medical Ethics Committee of the Hospital (Approval Number: 2019 Medical Ethics Review No. 67). Results:Eight cases of GA1 were diagnosed among the 814 625 neonates. Blood glutaryl carnitine (C5DC) and urine glutaric acid (GA) levels of the 8 children were higher than the normal reference values. In total 12 variants were detected, all of which were missense variants. c. 1064G>A (p.Arg355His) was the most common one, accounting for 21.4% (3/14). Three GCDH gene variants, including 1297G>C (p.Ala433Pro), c. 467G>A (p.Gly156Asp) and c. 1125T>G (p.Cys375Trp), were previously unreported. REVEL software analysis predicted that all of the three variants were harmful. 3D protein structure modeling indicated that the three variants may cause amino acid residue alterations, and c. 1297G>C (p.Ala433Pro) and c. 1125T>G (p.Cys375Trp) may result in increase in hydrogen bonds and may affect the function of GCDH protein. By December 2023, one of the eight children had deceased, and another child had severe clinical symptoms with poor prognosis. Six children had a good prognosis, of which two had mild motor development delay and four had normal development without clinical symptoms. Conclusion:The incidence of GA1 in newborns screened by MS/MS in Henan Province is 1/101 828, and the carrier rate of pathogenic GCDH variants is 1/160. The c. 1064G>A (p.Arg355His) may be the hotspot variant of the GCDH gene among children with GA1 in Henan. Discovery of the three novel variants has enriched the mutational spectrum of the GCDH gene and provide a basis for the early diagnosis, treatment, prognosis and genetic counseling of this disease.

OBJECTIVE: To explore the incidence, clinical features, genetic variant characteristics and prognosis of Glutaric acidemia type I (GA1) among neonates from Henan Province. METHODS: A total of 814 625 neonates undergoing screening for inherited metabolic diseases by tandem mass spectrometry (MS/MS) at the Third Affiliated Hospital of Zhengzhou University from January 2016 to December 2022 were selected as the study subjects. A retrospective method was adopted to collect the clinical data of the patients. Whole exome sequencing was carried out to detect GCDH gene variants in individuals with positive results by GA1 newborn screening, and Sanger sequencing was used to verify the candidate variants. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the pathogenicity of candidate variants was rated. This study was approved by the Medical Ethics Committee of the Hospital (Ethics Number: 2019 Medical Ethics Review No. 67). RESULTS: Eight cases of GA1 were diagnosed among the 814 625 neonates. Blood glutaryl carnitine (C5DC) and urine glutaric acid (GA) levels of the 8 children were higher than the normal reference values. In total 12 variants were detected, all of which were missense variants. c.1064G>A (p.Arg355His) was the most common one, accounting for 21.4% (3/14). Three GCDH gene variants, including 1297G>C (p.Ala433Pro), c.467G>A (p.Gly156Asp) and c.1125T>G (p.Cys375Trp), were previously unreported. REVEL software analysis predicted that all of the three variants were harmful. 3D protein structure modeling indicated that the three variants may cause amino acid residue alterations, and c.1297G>C (p.Ala433Pro) and c.1125T>G (p.Cys375Trp) may result in increase in hydrogen bonds and affect the function of GCDH protein. By December 2023, one of the eight children had deceased, and another child had severe clinical symptoms with poor prognosis. Six children had a good prognosis, of which two had mild motor development delay and four had normal development without clinical symptoms. CONCLUSION The incidence of GA1 in newborns screened by MS/MS in Henan Province is 1/101 828, and the carrier rate of pathogenic GCDH variants is 1/160. The c.1064G>A (p.Arg355His) may be the hotspot variant of the GCDH gene among children with GA1 in Henan. Discovery of the three novel variants has enriched the mutational spectrum of the GCDH gene and provide a basis for the early diagnosis, treatment, prognosis and genetic counseling of this disease.
Humans ; Amino Acid Metabolism, Inborn Errors/epidemiology* ; Glutaryl-CoA Dehydrogenase/chemistry* ; Infant, Newborn ; Female ; Neonatal Screening/methods* ; Male ; Brain Diseases, Metabolic/epidemiology* ; China/epidemiology* ; Retrospective Studies ; Mutation ; Genetic Variation ; Glutarates

Objective To investigate the value of MRI of the sternal end of clavicle in bone age assessment in Chinese population,especially its applicability in the determination of criminal responsible age.Methods A total of 431 patients aged from 10.00 to 29.99 years with neck or chest MRI were retrospectively collected.According to the Schmeling grading method,the epiphyseal development of the clavicle MRI was divided into five grades.The consistency of methods was evaluated.The correlation and general descriptive analysis between MRI grades and age was analyzed.The sex difference was analyzed.Curve fitting was used to establish a nonlinear model between age and grades.Results The grades of clavicle MRI showed a significant age-related trend(Figure 2),and the correlation was 0.861(0.887 in males and 0.840 in females).Except for grade 1,there was no significant difference between males and females in other grades.The minimum age of male grade 3 was greater than 14 years old,and the minimum age of female grade 3 was greater than 16 years old.The minimum age in grade 4 and grade 5 was over 18 years old in both sexes.The best curve fitting model was cubic model for both sexes(R2=0.805 for men and 0.722 for women).Conclusion Clavicle MRI can be used for the assessment of bone age in Chinese population.Complete epiphyseal plate closure can be used as a reliable indicator for the determination of age at 18 years old,and it is expected to achieve radiation-free forensic bone age assessment.

Objective To investigate the value of MRI of the sternal end of clavicle in bone age assessment in Chinese population,especially its applicability in the determination of criminal responsible age.Methods A total of 431 patients aged from 10.00 to 29.99 years with neck or chest MRI were retrospectively collected.According to the Schmeling grading method,the epiphyseal development of the clavicle MRI was divided into five grades.The consistency of methods was evaluated.The correlation and general descriptive analysis between MRI grades and age was analyzed.The sex difference was analyzed.Curve fitting was used to establish a nonlinear model between age and grades.Results The grades of clavicle MRI showed a significant age-related trend(Figure 2),and the correlation was 0.861(0.887 in males and 0.840 in females).Except for grade 1,there was no significant difference between males and females in other grades.The minimum age of male grade 3 was greater than 14 years old,and the minimum age of female grade 3 was greater than 16 years old.The minimum age in grade 4 and grade 5 was over 18 years old in both sexes.The best curve fitting model was cubic model for both sexes(R2=0.805 for men and 0.722 for women).Conclusion Clavicle MRI can be used for the assessment of bone age in Chinese population.Complete epiphyseal plate closure can be used as a reliable indicator for the determination of age at 18 years old,and it is expected to achieve radiation-free forensic bone age assessment.

Objective:To explore the incidence, clinical features, genetic variant characteristics and prognosis of Glutaric acidemia type I (GA1) among neonates from Henan Province.Methods:A total of 814 625 neonates undergoing screening for inherited metabolic diseases by tandem mass spectrometry (MS/MS) at the Third Affiliated Hospital of Zhengzhou University from January 2016 to December 2022 were selected as the study subjects. A retrospective method was adopted to collect the clinical data of the patients. Whole exome sequencing was carried out to detect GCDH gene variants in individuals with positive results by GA1 newborn screening, and Sanger sequencing was used to verify the candidate variants. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the pathogenicity of candidate variants was rated. This study was approved by the Medical Ethics Committee of the Hospital (Approval Number: 2019 Medical Ethics Review No. 67). Results:Eight cases of GA1 were diagnosed among the 814 625 neonates. Blood glutaryl carnitine (C5DC) and urine glutaric acid (GA) levels of the 8 children were higher than the normal reference values. In total 12 variants were detected, all of which were missense variants. c. 1064G>A (p.Arg355His) was the most common one, accounting for 21.4% (3/14). Three GCDH gene variants, including 1297G>C (p.Ala433Pro), c. 467G>A (p.Gly156Asp) and c. 1125T>G (p.Cys375Trp), were previously unreported. REVEL software analysis predicted that all of the three variants were harmful. 3D protein structure modeling indicated that the three variants may cause amino acid residue alterations, and c. 1297G>C (p.Ala433Pro) and c. 1125T>G (p.Cys375Trp) may result in increase in hydrogen bonds and may affect the function of GCDH protein. By December 2023, one of the eight children had deceased, and another child had severe clinical symptoms with poor prognosis. Six children had a good prognosis, of which two had mild motor development delay and four had normal development without clinical symptoms. Conclusion:The incidence of GA1 in newborns screened by MS/MS in Henan Province is 1/101 828, and the carrier rate of pathogenic GCDH variants is 1/160. The c. 1064G>A (p.Arg355His) may be the hotspot variant of the GCDH gene among children with GA1 in Henan. Discovery of the three novel variants has enriched the mutational spectrum of the GCDH gene and provide a basis for the early diagnosis, treatment, prognosis and genetic counseling of this disease.

Objective:To explore the prevalence, clinical features, genetic characteristics and prognosis of Citrin deficiency in Henan province of China.Methods:A total of 986 565 neonates screened by tandem mass spectrometry at the Third Affiliated Hospital of Zhengzhou University from January 2013 to December 2021 were retrospectively analyzed. Analysis of SLC25A13 gene variants and parental verification were carried out for neonates suspected for Citrin deficiency by next-generation sequencing. The clinical, biochemical and genetic characteristics of Citrin deficiency patients were integrated to guide the diet treatment and follow up the growth and development. Paired- t test was used to compare the amino acid levels in the peripheral blood samples before and after the treatment. Results:Nine cases of Citrin deficiency were diagnosed among the 986 565 neonates. Specific elevation of citrulline was observed in all of the 9 cases. Six variants were detected by genetic sequencing, among which c. 852_855delTATG, c. 615+ 5G>A, c. 550C>T and IVS16ins3kb were known pathogenic variants, whilst c. 1111_1112delAT and c. 837T>A were unreported previously. The detection rate for c. 852_855delTATG was the highest (61.6%, 11/18), followed by IVS16ins3kb (16.7%, 3/18). The clinical symptoms of all patients were relieved after the treatment, and the blood amino acid profile and biochemical parameters were significantly improved by gradually falling within the normal range. By June 2022, all patients had shown a good prognosis.Conclusion:The prevalence of Citrin deficiency among neonates from Henan Province by tandem mass spectrometry is 1/109 618, and the carrier rate for the pathogenic variants of the SLC25A13 gene was 1/166. The c. 852_855delTATG may be a hot spot variant among the patients. Discovery of the novel variants has enriched the mutational spectrum of the SLC25A13 gene. Above results have provided a basis for the early diagnosis, treatment, prognosis and genetic counseling for the affected families.

Objective:To standardize the quantitation of 18F-Florbetapir PET SUV ratio (SUVR) to the Centiloid (CL) scale, and analyze the positive rate of β-amyloid (Aβ) in Chinese Preclinical Alzheimer′s Disease (AD) Study (C-PAS). Methods:11C-Pittsburgh compound B(PIB) and 18F-Florbetapir images from public databases " Standard PIB" and " Florbetapir Calibration" were preprocessed by statistical parametric mapping (SPM) 12, and the transformative formulas from SUVR to CL were derived. Then a total of 942 subjects (357 males, 585 females; age (66.4±8.1) years) from C-PAS who received 18F-Florbetapir PET at the Department of Nuclear Medicine & PET Center, Huashan Hospital, Fudan University from October 2018 to August 2023 were retrospectively included. CL values were calculated and the Aβ positive rates (CL value≤12, Aβ negative; 12< CL value<30, Aβ subtle pathology; CL value≥30, Aβ positive) of AD, mild cognitive impairment (MCI) and cognitive unimpaired (CU) groups were explored. Data were analyzed by using Kruskal-Wallis rank sum test, Dunn′s test (Bonferroni correction ) and χ2 test. Results:The formula for the 18F-Florbetapir SUVR converted to CL was CL=179.64×SUVR_Florbetapir-186.95. In the C-PAS cohort, the SUVR, CL value, Aβ positive rate (including subtle pathology) of patients with clinically diagnosed AD were 1.29±0.22, 43.97±39.23, 71.80%(140/195), which were 1.04(1.02, 1.14), 1.16(-4.04, 17.14), 28.50%(61/214) for patients with MCI, and 1.04(1.01, 1.08), 0.54(-5.29, 7.69), 15.38%(82/533) for CU subjects, respectively. SUVR, CL value and the ratio of negative, subtle and positive Aβ pathology of the above three groups exhibited statistical differences ( H=148.30, H=148.30, χ2=262.12, all P<0.001). Besides, mixed MCI group exhibited higher CL values ((2.45(-1.54, 46.32) vs -1.58(-6.33, 7.20); H=8.21, P=0.016; z=2.81, P=0.015) and Aβ positive rate (including subtle pathology) (41.18%(14/34) vs 14.64%(6/41); χ2 values: 12.71 and 10.63, both P<0.01), compared to non-amnestic MCI group. The CL values and Aβ positive rates were also increased with age in CU group. Conclusion:This study validates the feasibility of the CL formula with 18F-Florbetapir images and reveals Aβ deposition in C-PAS cohort, which can lay the foundation for multi-center Aβ PET studies in China.

Objective:To compare the localization accuracy of interictal 18F-FDG and 18F-flumazenil (FMZ) PET/CT imaging for focal cortical dysplasia (FCD). Methods:A retrospective analysis was conducted on 22 patients (12 males, 10 females; age 8-36 years) with pathologically confirmed FCD who underwent surgical resection at Huashan Hospital, Fudan University from July 2021 to June 2023. All patients underwent 18F-FDG and 18F-FMZ PET/CT scans before surgery. Surgical pathological diagnosis was used as the gold standard. Visual scoring was used to analyze the images. The accuracy of the two imaging methods in the localization of FCD was compared, and subgroup analysis (FCD Ⅱa, FCD Ⅱb) of different pathological type was further performed. Paired- t test, χ2 test or Fisher′s exact test was used to analyze the data. Results:The visual score of 18F-FMZ PET/CT was higher than that of 18F-FDG (3.00±0.82 vs 2.27±0.92; t=4.17, P=0.020). The accuracy of interictal 18F-FMZ PET/CT was 77.27%(17/22), which was higher than that of 18F-FDG PET/CT (36.36%, 8/22; χ2=7.50, P=0.006). Subgroup analysis showed that within the cohort of patients diagnosed with FCD Ⅱa ( n=18), 18F-FMZ PET/CT outperformed 18F-FDG in terms of accuracy for localization (15/18 vs 6/18; P=0.006). Conclusion:Compared to 18F-FDG, 18F-FMZ PET/CT demonstrates clearer and more accurate identification of lesion borders, and exhibits higher precision, which provides valuable guidance for preoperative localization.

Objective:Analyzing the influence of morphological evaluation parameters of blastocysts, including days of blastocyst development [day 5 (D5) and day 6 (D6)], degree of blastocyst expansion (4, 5, 6), inner cell mass and trophectoderm grade, on the occurrence of chromosomal karyotype abnormalities of chorionic villi in missed abortion after in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) treatment and fresh/frozen-thawed single blastocyst transfer. Methods:The clinical data of patients with missed abortion after IVF/ICSI treatment and fresh/frozen-thawed single blastocyst transfer from February 2015 to February 2023 in the Reproductive Center of the Third Affiliated Hospital of Zhengzhou University were included. Using a case-control study, the data were divided into two groups according to the detection results of chromosomal copy number variations (CNVs) in chorionic villi of missed abortion abnormal karyotype group ( n=139) and normal karyotype group ( n=82). The baseline data between the two groups were compared. Univariate logistic regression was used to investigate the effect of blastocyst morphological rating parameters on the occurrence of chromosomal karyotype abnormalities of chorionic villi in aborted tissues, and multivariate logistic regression was also used to adjust confounding factors. Results:Male age [(34.12±6.49) years], sperm morphology rate [5.00 (4.00,6.00)%] and female age [33.00 (30.00, 37.00) years] in abnormal karyotype group were higher than those in the normal karyotype group [(32.38±4.69) years, 4.00 (2.00,5.00)% and 31.50 (29.00,34.00) years], and the differences were statistically significant ( P=0.022, P=0.020, P=0.009). Univariate and multivariate logistic regression analyses showed that days of blastocyst development, degree of blastocyst expansion, inner cell mass and trophectoderm grade did not increase the risk of chromosomal karyotype abnormalities of chorionic villi (all P>0.05). Conclusion:There is no significant correlation between blastocyst morphological evaluation parameters and chromosomal karyotype abnormalities in chorionic villi of missed abortion after fresh/frozen-thawed single blastocyst transfer with IVF/ICSI treatment.

Objective:Analyzing the influence of morphological evaluation parameters of blastocysts, including days of blastocyst development [day 5 (D5) and day 6 (D6)], degree of blastocyst expansion (4, 5, 6), inner cell mass and trophectoderm grade, on the occurrence of chromosomal karyotype abnormalities of chorionic villi in missed abortion after in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) treatment and fresh/frozen-thawed single blastocyst transfer. Methods:The clinical data of patients with missed abortion after IVF/ICSI treatment and fresh/frozen-thawed single blastocyst transfer from February 2015 to February 2023 in the Reproductive Center of the Third Affiliated Hospital of Zhengzhou University were included. Using a case-control study, the data were divided into two groups according to the detection results of chromosomal copy number variations (CNVs) in chorionic villi of missed abortion abnormal karyotype group ( n=139) and normal karyotype group ( n=82). The baseline data between the two groups were compared. Univariate logistic regression was used to investigate the effect of blastocyst morphological rating parameters on the occurrence of chromosomal karyotype abnormalities of chorionic villi in aborted tissues, and multivariate logistic regression was also used to adjust confounding factors. Results:Male age [(34.12±6.49) years], sperm morphology rate [5.00 (4.00,6.00)%] and female age [33.00 (30.00, 37.00) years] in abnormal karyotype group were higher than those in the normal karyotype group [(32.38±4.69) years, 4.00 (2.00,5.00)% and 31.50 (29.00,34.00) years], and the differences were statistically significant ( P=0.022, P=0.020, P=0.009). Univariate and multivariate logistic regression analyses showed that days of blastocyst development, degree of blastocyst expansion, inner cell mass and trophectoderm grade did not increase the risk of chromosomal karyotype abnormalities of chorionic villi (all P>0.05). Conclusion:There is no significant correlation between blastocyst morphological evaluation parameters and chromosomal karyotype abnormalities in chorionic villi of missed abortion after fresh/frozen-thawed single blastocyst transfer with IVF/ICSI treatment.