Objective: To retrospectively analyze the prevalence of hepatitis C virus (HCV) infection among voluntary blood donors in Qinghai Province over a ten-year period and to provide evidence for refining blood safety screening strategies. Methods: Blood samples from 362 066 blood donors in Qinghai collected between January 2015 and April 2024 were simultaneously screened using enzyme-linked immunosorbent assay (ELISA) and nucleic acid testing (NAT). Follow-up was conducted for donors with reactive HCV RNA screening results, and alanine transaminase (ALT) was detected by rate method. Results: The HCV positive rate among blood donors in Qinghai was 0.22%. Gender, marital status, number of blood donations, and educational level were associated with HCV infection. Significant differences in HCV positive rates were observed among donors across regions and ethnic groups. The HCV positive rate among donors in Golog Tibetan Autonomous Prefecture (with an average altitude of 4 330 m) was significantly higher than that in Xining (0.52% vs 0.21%, P<0.001). Positivity rates were also significantly higher in Salar (0.84%), Hui (0.81%), Zang (0.60%), and Tu (0.45%) ethnic groups compared to the Han ethnic group (0.17%) (P<0.001). The abnormal rate of ALT in HCV-positive donors was higher than in non-HCV donors (6.13% vs 1.55%) (P<0.001). Conclusion: The relatively high HCV positivity rate among blood donors in Qinghai highlights the need for further investigation into viral sources, risk factors, and transmission routes. Optimized screening strategies are essential to ensure blood safety.

Objective To analyze the clinical manifestations and genetic etiology of three families with hereditary spastic paraplegia(HSP).Methods Gene analysis was performed on patients of the three HSP families from the Gansu Provincial Maternity and Child-care Hospital.Results The proband of family 1 was autosomal recessive spastic paraplegia type 35 caused by homozygous variant c.159_176delGGCGGGCCAGGACATCAG(p.Arg53_Ser59delinsSer)in FA2H.The proband in family 2 was autosomal recessive spastic paraplegia type 47 caused by homozygous variant c.1399G>T(p.Glu467Ter)in AP4B1,and the proband in family 3 was autosomal recessive spastic paraplegia type 11 caused by homozygous variation c.7023C>G(p.Tyr2341Ter)in SPG11.Among them,the variant c.1399G>T(p.Glu467Ter)of AP4B1 is a novel variant,that has not been reported before,according to the ACMG guidelines,the pathogenicity of this variant is pathogenic.Conclusion This study has expanded the variant spectrum of AP4B1 which provides basic data to improve clinical understanding and diagnostic capabilities of HSP patients.

Objective To analyze the clinical manifestations and genetic etiology of three families with hereditary spastic paraplegia(HSP).Methods Gene analysis was performed on patients of the three HSP families from the Gansu Provincial Maternity and Child-care Hospital.Results The proband of family 1 was autosomal recessive spastic paraplegia type 35 caused by homozygous variant c.159_176delGGCGGGCCAGGACATCAG(p.Arg53_Ser59delinsSer)in FA2H.The proband in family 2 was autosomal recessive spastic paraplegia type 47 caused by homozygous variant c.1399G>T(p.Glu467Ter)in AP4B1,and the proband in family 3 was autosomal recessive spastic paraplegia type 11 caused by homozygous variation c.7023C>G(p.Tyr2341Ter)in SPG11.Among them,the variant c.1399G>T(p.Glu467Ter)of AP4B1 is a novel variant,that has not been reported before,according to the ACMG guidelines,the pathogenicity of this variant is pathogenic.Conclusion This study has expanded the variant spectrum of AP4B1 which provides basic data to improve clinical understanding and diagnostic capabilities of HSP patients.

Objective:To explore the genetic basis of eighteen patients with tetrahydrobiopterin deficiency (BH4D) from Gansu Province.Methods:Eighteen patients diagnosed with BH4D at Gansu Provincial Maternal and Child Health Care Hospital from January 2018 to December 2021 were selected as the study subjects. Whole exome sequencing was carried out, and candidate variants were verified by Sanger sequencing.Results:All of the thirty-six alleles of the eighteen patients were successfully determined by molecular genetic testing. Sixteen patients were found to harbor variants of the PTS gene, and two had harbored variants of the QDPR gene. Ten variants were detected in the PTS gene, with the most common ones being c. 259C>T (34.38%) and c. 286G>A (15.63%). Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the c. 259C>T was classified as a pathogenic variant, whilst the c. 286G>A, c. 166G>A, c. 200C>T, c. 272A>G, c. 402A>C, c. 421G>T, c. 84-291A>G and c. 317C>T were classified as likely pathogenic variants. A novel c. 289_290insCTT variant was classified as likely pathogenic (PM1+ PM2_Supporting+ PM3+ PP3+ PP4). The two variants (c.478C>T and c. 665C>T) detected in the QDPR gene were both classified as variants of uncertain significance (PM1+ PM2_Supporting+ PP3+ PP4). Conclusion:Genetic testing has clarified the pathogenic variants in these BH4D patients, which has enabled timely and accurate clinical intervention and treatment, and provided a reference for genetic counseling and reproductive guidance for their families.

Objective:To explore the genetic basis for a Chinese pedigree affected with co-morbid Ornithine carbamoyl transferase deficiency (OTCD) and MECP2 duplication syndrome.Methods:A proband who was admitted to the Neonatal Intensive Care Unit of Gansu Provincial Maternal and Child Health Care Hospital on December 19, 2017 was selected as the study subject. High-throughput sequencing and multiplex ligation-dependent probe amplification (MLPA) were carried out for her pedigree, and short tandem repeat-based linkage analysis and chromosome copy number variation sequencing (CNV-seq) were used for the prenatal diagnosis.Results:The proband, a 3-day-old female, was found to harbor heterozygous deletion of exons 7-9 of the OTC gene. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was classified as likely pathogenic (PVS1+ PM2_Supporting+ PP4). The proband was diagnosed with OTCD, which was in keeping with her acute encephalopathy and metabolic abnormalities (manifesting as hyperammonemia, decreased blood citrulline, and increased urine orotic acid). Prenatal diagnosis was carried out for the subsequent pregnancy. The fetus did not harbor the exons 7-9 deletion of the OTC gene, but was found to carry a duplication in Xq28 region (which encompassed the whole region of MECP2 duplication syndrome) and was positive for the SRY sequence. The same duplication was also found in the proband and her mother. Considering the possible existence of X-chromosome inactivation, the proband was diagnosed with two X-linked recessive disorders including OTCD and MECP2 duplication syndrome, and the fetus was determined as a male affected with the MECP2 duplication syndrome. Conclusion:Discoveries of the pathogenic variants underlying the OTCD and MECP2 duplication syndrome have enabled clinical intervention, treatment, genetic counseling and prenatal diagnosis for this pedigree.

Objective:To explore the genetic basis for a patient with autosomal dominant retinitis pigmentosa (RP).Methods:A male patient with RP treated at Gansu Provincial Maternal and Child Health Care Hospital in September 2019 was selected as the study subject. Clinical data was collected. Peripheral blood samples of the patient and his parents were subjected to whole exome sequencing (WES). Candidate variant was validated by Sanger sequencing and bioinformatic analysis.Results:The patient, a 29-year-old male, developed night blindness, amblyopia, visual field defects and optic disc abnormalities since childhood. Gene sequencing revealed that he has harbored a heterozygous c. 942G>C (p.Lys314Asn) variant of the IMPDH1 gene, which was inherited from his mother, whilst his father was of the wild type. Based on the guidelines from the American College of Medical Genetics and Genomics, the c. 942G>C variant was predicted as likely pathogenic (PM1+ PM2_Supporting+ PP3+ PP1). Conclusion:The c. 942G>C (p.Lys314Asn) variant in the IMPDH1 gene probably underlay the RP in this patient.

Objective:To analyze the clinical phenotype and genotypes of two children with Carnitine-acylcarnitine translocase deficiency (CACTD).Methods:Two children diagnosed with CACTD at the Gansu Provincial Maternal and Child Health Care Hospital respectively on January 3 and November 19, 2018 were selected as the study subjects. Trio-whole exome sequencing (trio-WES) was carried out, and candidate variants were validated through Sanger sequencing and pathogenicity analysis.Results:Both children were males and had manifested mainly with hypoglycemia. Trio-WES and Sanger sequencing showed that child 1 had harbored compound heterozygous variants of the SLC25A20 gene, namely c. 49G>C (p.Gly17Arg) and c. 106-2A>G, which were inherited from his father and mother, respectively. Child 2 had harbored homozygous c. 199-10T>G variants of the SLC25A20 gene, which were inherited from both of his parents. Among these, the c. 106-2A>G and c. 49G>C variants were unreported previously. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the c. 49G>C (p.Gly17Arg), c. 106-2A>G, and c. 199-10T>G variants were classified as likely pathogenic (PM2_supporting+ PP3+ PM3_strong+ PP4), pathogenic (PVS1+ PM2_supporting+ PM5+ PP3), and pathogenic (PVS1+ PM2_supporting+ PP3+ PP5), respectively. Conclusion:Combined with their clinical phenotype and genetic analysis, both children were diagnosed with CACTD. Above finding has provided a basis for their treatment as well as genetic counseling and prenatal diagnosis for their families.

Objective To study the action and mechanism of Sancai Lianmei Particle on cell apoptosis of liver cells in Type 2 Diabetes Mellitus(T2DM)combined with Non-alcoholic Fatty Liver Disease(NAFLD).Methods High fat and sugar + STZ induced diabetic with fatty liver rats used as models,intervention with Sancai Lianmei Particle,intraperitoneal glucose tolerance test(IPGTT)to assess insulin resistance,ELISA method to detect the mice serum biochemistry,insulin levels;ELISA method to detect inflammatory factors in liver homogenate;SOD and MDA levels were monitored to assess the degree of oxidative stress;ASK1/JNK/NF-κB mRNA expression in liver tissue was monitored by Real-time PCR;apoptotic-related proteins were detected by Western blot,apoptosis of hepatocytes was assayed by TUNEL;HE staining was conducted to observe the liver tissue.Results Sancai Lianmei Particle can obviously reduce the body weight of T2DM with NAFLD model rats;reduce the levels of GHb,INS,TC,TG,LDL-C,ALT,AST,IL-1β,IL-6,TNF-α,MDA;improve insulin resistance and oxidative stress.HE staining of liver tissue showed that Sancai Lianmei Particle could alleviate the vacuolar degeneration of liver and deposition of lipid droplets.Sancai Lianmei Particle can effectively down-regulate the expressions of ASK1,JNK and NF-κB mRNA in liver tissues of model rats.Western Blot results exhibited that Sancai Lianmei Particle could significantly regulate the expression of apoptotic proteins of Bax,Caspase-3,and Bcl-2 and inhibit the apoptosis of hepatocytes.Conclusion This study proved that Sancai Lianmei Particle can improve hepatic insulin resistance and oxidative stress,slow the progression of NAFLD by regulating liver cell apoptosis based on ROS-ASK1-JNK/NF-κB pathway.

We retrospectively analyzed a child with early-onset globoid cell leukodystrophy(Krabbe's disease)caused by complex heterozygous variations in the GALC gene.The girl was admitted to the hospital at the age of 4 month with main complaints of"No obvious cause of milk refusal,poor mental state,drowsiness,convulsions,fever."Brain MRI showed abnormal symmetric signals changes in bilateral cerebellar hemispheres,bilateral internal capsule hind limbs and bilateral ventricles,thin corpus callosum,myelination process lags behind the level of children of the same age.High-throughput sequencing analysis identified compound heterozygous mutations in GALC gene(NM 000153.4):c.[908+1G>A];[194G>A and the two heterozygous mutations were correspondingly inherited from his father and mother,respectively.The application of high-throughput sequencing technology can diagnose Krabbe disease efficiently and accurately,which assists in clinical identification and diagnosis.

OBJECTIVE: To explore the genetic etiology of a child with Pitt-Hopkins syndrome. METHODS: A child who had presented at the Medical Genetics Center of Gansu Provincial Maternal and Child Health Care Hospital on February 24, 2021 and his parents were selected as the study subjects. Clinical data of the child was collected. Genomic DNA was extracted from peripheral blood samples of the child and his parents and subjected to trio-whole exome sequencing (trio-WES). Candidate variant was verified by Sanger sequencing. Karyotype analysis was also carried out for the child, and her mother was subjected to ultra-deep sequencing and prenatal diagnosis upon her subsequent pregnancy. RESULTS: The clinical manifestations of the proband included facial dysmorphism, Simian crease, and mental retardation. Genetic testing revealed that he has carried a heterozygous c.1762C>T (p.Arg588Cys) variant of the TCF4 gene, for which both parents had a wild-type. The variant was unreported previously and was rated as likely pathogenic based on the guidelines of the American College of Medical Genetics and Genomics (ACMG). Ultra-deep sequencing indicated that the variant has a proportion of 2.63% in the mother, suggesting the presence of low percentage mosaicism. Prenatal diagnosis of amniotic fluid sample suggested that the fetus did not carry the same variant. CONCLUSION The heterozygous c.1762C>T variant of the TCF4 gene probably underlay the disease in this child and has derived from the low percentage mosaicism in his mother.
Child ; Female ; Humans ; Male ; Pregnancy ; Intellectual Disability/genetics* ; Mosaicism ; Mothers ; Mutation ; Parents ; Transcription Factor 4/genetics*