OBJECTIVE: To investigate the clinical characteristics and genetic etiology of a child with Cortical dysplasia, complex, with other brain malformations 4 (CDCBM4) and epilepsy due to a TUBG1 gene variant. METHODS: A child diagnosed with CDCBM4 and epilepsy at the Children's Medical Center of the Affiliated Hospital of Guangdong Medical University in May 2024 was selected as the study subject. Clinical data were retrospectively analyzed. Peripheral venous blood samples were collected from the child and her parents for genomic DNA extraction. Trio-based whole-exome sequencing (WES) was performed, and candidate variants were validated by Sanger sequencing. According to the Standards and Guidelines for the Interpretation of Sequence Variants established by the American College of Medical Genetics and Genomics (ACMG), candidate variants were classified for pathogenicity. This study was approved by the Medical Ethics Committee of the Affiliated Hospital of Guangdong Medical University (Ethics No.: PJ2021-097). RESULTS: The child, a 4-month-old female infant, had no special facial features, normal limb muscle strength, and increased muscle tone of infantile onset, with generalized tonic-clonic seizures as the main manifestation. During seizures, she exhibited head retroflexion, tightly closed eyes, and tonic convulsions of the limbs, occurring approximately 2-3 times per day. Electroencephalogram suggested bilateral anterior predominant medium-to-high amplitude 7-8 Hz mixed rhythm discharges. Head MRI revealed ventricular system dilatation and pachygyria. Trio-WES results indicated that the child has harbored a TUBG1 gene variant of c.776C>T (p.Ser259Leu). Sanger sequencing verification showed that neither of her parents had carried the same variant, confirming it as de novo in origin. According to the ACMG guidelines, the variant was rated as pathogenic (PS2+PS3+PM2_Supporting+PP3). Combining the child's clinical phenotype, the child was diagnosed as CDCBM4 with epilepsy. CONCLUSION Children with CDCBM4 and epilepsy due to TUBG1 gene variants may show pachygyria or agyria and commonly present with intellectual and motor developmental delays and seizure disorders of variable severity. The heterozygous TUBG1 c.776C>T (p.Ser259Leu) variant is likely the genetic etiology underlying this disorder. The results of this study has expanded the mutational spectrum of the TUBG1 gene associated with CDCBM4 and epilepsy.
Humans ; Female ; Epilepsy/genetics* ; Malformations of Cortical Development/genetics* ; Infant ; Phenotype ; Exome Sequencing ; Microtubule-Associated Proteins/genetics*

OBJECTIVE: To explore the clinical phenotype and genetic etiology of a child with Ehlers-Danlos syndrome, spondylodysplastic type 2 (EDSSPD2). METHODS: A child who was admitted to the Children's Medical Center of the Affiliated Hospital of Guangdong Medical University in July 2024 for "delayed motor development for 1 and a half year" was selected as the study subject. Clinical data of the child was collected, including medical history, family history, and results of auxiliary examinations. Peripheral venous blood samples were collected from the child and his two brothers and both parents. Genomic DNA was extracted from the child and his family members and subjected to whole-exome sequencing (WES) and copy number variation (CNV) analysis. Sanger sequencing was used to verify the parental origin of the candidate variants. Multiple protein function prediction software tools, including SIFT, PolyPhen-2, and REVEL, were used to assess the impact of candidate variants on the protein function. Based on protein database information from UniProt, a two dimensional structural schematic of the target protein was generated. The pathogenicity of the variants was classified based on the guidelines from the American College of Medical Genetics and Genomics (ACMG). Relevant literature on the B3GALT6 gene variants leading to EDSSPD2 was retrieved from CNKI, Wanfang Data Knowledge Service Platform, and PubMed databases. The procedures followed in this study were reviewed and approved by the Medical Ethics Committee of Affiliated Hospital of Guangdong Medical University (Ethics No.：PJ2021-097). RESULTS: The proband was a 2-year-old male with an onset in infancy. The main clinical manifestations included loose skin, scoliosis and kyphosis, generalized hypermobility of joints, and motor developmental delay. WES has revealed two compound heterozygous variants of the B3GALT6 gene (NM_080605.4): c.766C>T (p.Arg256Trp) and c.962G>A (p.Cys321Tyr). Sanger sequencing verification showed that the c.766C>T and c.962G>A variants were respectively derived from his phenotypically normal father and mother. Bioinformatics analysis showed that for the c.766C>T (p.Arg256Trp) variant, the Arg256 site is located within the galactosyltransferase catalytic domain (GalT domain) of the β3GalT6 protein. According to the ACMG guidelines, the c.766C>T variant was classified as a likely pathogenic (PS3+PM2_supporting+PM3+PP3), and the c.962G>A was classified as a variant of unknown significance (PM2_Supporting+PM3+PP3). By following the pre-set literature retrieval strategy, a total of 12 articles related to B3GALT6 gene variants were identified (11 English and 1 Chinese), which involved a total of 71 patients. Among these, 4 reports (involving 20 patients) involved B3GALT6 gene variants leading to EDSSPD2. Among the 18 live-born EDSSPD2 patients (including the proband in this study), common clinical manifestations have included scoliosis (88.9%, 16/18), generalized hypotonia (83.3%, 15/18), and soft and lax skin (66.7%, 12/18). Some patients already showed skeletal abnormalities on prenatal ultrasound scan (22.2%, 4/18), while a few presented with cervical instability (16.7%, 3/18). One child had deceased at 18 months of age due to hypoxia caused by tracheomalacia and tracheal compression due to scoliosis. Among the 23 reported EDSSPD2 related B3GALT6 variant sites, missense variants were the most common (78.3%, 18/23), followed by nonsense variants (21.7%, 5/23). CONCLUSION Above finding has enriched the clinical and mutational spectra of EDSSPD2. Early genetic testing has important clinical value for the diagnosis, differential diagnosis, and genetic counseling of this disease.
Humans ; Male ; Ehlers-Danlos Syndrome/genetics* ; Pedigree ; N-Acetylgalactosaminyltransferases/genetics* ; Asian People/genetics* ; DNA Copy Number Variations ; Exome Sequencing ; Female ; Child ; Child, Preschool ; Phenotype ; Mutation ; China ; East Asian People ; Galactosyltransferases

Objective To investigate the unmet needs for assistive technology for people with physical disabilities in Chengdu,and analyze the related factors. Methods From November,2023 to March,2024,the persons with physical disabilities in Chengdu were selected from Sichuan Individuation service platform,and investigated using World Health Organization rapid Assistive Tech-nology Assessment. Results A total of 558 questionnaires were set up,and 527 effective questionnaires retured.26.8%of them reported un-met needs for aids,with the highest need for mobility aids(66.0%).Lack of support(54.9%),high price(26.3%)and lack of knowledge about aids(20.3%)were the main reasons for not obtaining the aids they needed.Loss of spouse(OR=3.615),serious mobility impairment(OR＞2.926)and serious self-care impairment(OR＞2.781)were the risks of unmet needs for aids. Conclusion It is important to popularize policies and products of aids,pay attention to personal adaptation for people with different barriers,and strengthen the service system,to meet the needs of people with disabilities.

Objective:To explore the clinical phenotype and genetic etiology of a child with Developmental epileptic encephalopathy type 104 (DEE 104).Methods:A child who had presented at the Children′s Medical Center of the Affiliated Hospital of Guangdong Medical University in February 2021 for recurrent seizures over 1 month was selected as the study subject. Clinical data of the child was collected. Peripheral blood samples of the child and his parents were collected and subjected to whole exome sequencing (WES). Candidate variant was verified by Sanger sequencing.Results:The child, a five-month-old male, had presented with frequent focal seizures with severe developmental retardation from infancy. Physical examination showed emaciation, microcephaly, oblique palpebral fissures, Stahl′s ears, and hypotonia in the limbs. Electroencephalogram revealed multi-focal sharp waves, slow waves and slow spinal waves. Cranial magnetic resonance imaging revealed enlargement of bilateral lateral ventricles and the third ventricle, along with widening of brain sulci, fissure and cisterna. WES revealed that he had harbored a heterozygous c. 2401C>T (p.His801Tyr) missense variant of the ATP6V0A1 gene. Sanger sequencing showed that both of his parents were of the wild type. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was predicted to be likely pathogenic (PS2+ PM2_Supporting+ PP3). The proband was diagnosed with DEE 104. Early treatment with sodium valproate has failed, but the child had become seizure free after the addition of levetiracetam and topiramate. He still had abnormal EEG discharges and severe psychomotor retardation. Combining our case and a review of literature, DEE104 is mainly caused by de novo heterozygous variants of the ATP6V0A1 gene with an autosomal dominant inheritance. The patients may show refractory epilepsy and severe global developmental delay from infancy. Conclusion:The c. 2401C>T (p.His801Tyr) variant probably underlay the DEE104 in this child.

Objective:To explore the clinical features and genetic basis for a child with Intellectual developmental disorder (IDD) and epilepsy.Methods:A child who was admitted to the Children′s Medical Center of the Affiliated Hospital of Guangdong Medical University in February 2021 was selected as the study subject. Clinical data of the child was collected. Peripheral blood samples of the child and her parents were collected and subjected to whole exome sequencing (WES). Candidate variant was verified by Sanger sequencing.Results:The patient, a 3-month-and-27-day female infant, had developed the symptoms in the neonatal period, which included severe developmental delay, respiratory difficulties and pauses, increased muscle tone of four limbs, feeding difficulty, and seizures. Cerebral MRI revealed bilateral cerebellar hypoplasia, and video EEG showed slightly increased sharp waves emanating predominantly from the right parietal, occipital, and posterior temporal regions. WES revealed that she has harbored a missense c. 3196G>A (p.Glu1066Lys) variant of the CLTC gene, which was confirmed to be de novo by Sanger sequencing. Based on the guideline from the American College of Medical Genetics and Genomics (ACMG), the variant was classified as likely pathogenic (PS2+ PM2_Supporting+ PP3). Conclusion:The c. 3196G>A (p.Glu1066Lys) missense variant of the CLTC gene probably underlay the pathogenesis in this child. Above finding has facilitated her diagnosis and treatment.

Objective To analyze the research status and predict the development trend of clinical comprehensive evaluation of drugs in China, and to provide reference for clinical comprehensive evaluation. Methods CNKI, Wanfang and VIP database were used to search the published articles of clinical comprehensive evaluation. Literature searching was set from the building time of the database to 2022, the basic information about the published articles was obtained for the evaluation of the literature quality. Bibliometrics and CiteSpace 6.1.R3 software were used to visualize the research authors, research institutions, and key words. Results After data screening, a total of 126 Chinese published articles were selected. The analysis showed that the numbers of published articles were rising continuously, and China Academy of Chinese Medical Sciences and Xie Yanming were the institute and the author with the maximum number of literatures, respectively. Conclusion The clinical comprehensive evaluation of drugs was conducted based on the clinical value of drugs, guided by the policy requirements. It is suggested that researchers should conduct the comprehensive evaluation according to the focus and requirements of government agencies, the pharmaceutical industry and the clinical applications.

Objective To assess of iron overload in thalassaemia minor patients and provide basis for clinical intervention.Methods A total of 458 thalassaemia minor patients confirmed by genetic tests were divided into two groups(α-thalassaemia group and β-thalassaemia group),and 120 healthy individuals were recruited into control group.Serum iron and serum ferritin were measured,correlations between serum ferritin and age,genotypes,hemoglobin were evaluated.Results There was no significant difference in serum iron among the three groups(P>0.05),but the differences of serum ferritin was statistically significant(P<0.05),and serum ferritin in the β-thalassemia group was higher than that of the α-thalassemia group(P<0.05).Serum ferritin also had significant differences between different age groups(P<0.05),and which was higher in young patients(≤20) and older patients.Besides that,in patients older than 20 years,the level of ferritin was positively correlated with age.Moreover,we found serum ferritin had statistically differences between genotypes in α-thalassaemia patients(P=0.006),and which had poor negatively correlation with hemoglobin in β-thalassaemia patients(r=-0.252,P=0.001).Conclusion Serum ferritin was a sensitive indicator to assess iron overload in thalassaemia minor patients,and which was positively correlated with age in thalassaemia patients 20 or more than 20 years old.Our research also indicates different iron overload traits between α-thalassaemia patients and β-thalassaemia patients.

Objective To understand the gene carrying rate ,gene mutation types and distribution characteristics of thalassemia in the northeast area of Chongqing .Methods 28 633 specimens collected from the patients and individuals with physical examina‐tion in our hospital from January to December 2013 were performed the RBC parameters detection and hemoglobin electrophoresis screening .The specimens with phenotype positive were definitely verified the thalassemia type by using Gap‐PCR and reverse dot blot(RDB) .Results Among 28 633 specimens ,1 358 specimens were finally diagnosed as thalassemia with the thalassemia carrying rate of 4 .74% ,including 589 cases(2 .06% ) of α‐thalassemia and 741 cases (2 .59% ) of β‐thalassemia cases .Among the α‐thalasse‐mia genotypes ,‐αα/‐‐SEA genotype(1 .38% ) was most common ,the next was ‐αα/‐α3 .7 genotype (0 .37% ) and αα/‐α4 .2 genotype (0 .20% ) .Among the β‐thalassemia genotypes ,CD41‐42 genotype (1 .27% ) had the highest constituent ratio ,followed by IVS‐2‐654 genotype(1 .27% ) and CD17 genotype(0 .30% ) .28 cases were found to be the double heterozygote with α‐thalassemia and β‐thalassemia .Conclusion The northeast area of Chongqing is a region with the high incidence rate of thalassemia and complicated heredity .Therefore this research provides the reference information for the prevention of thalassemia ,genetic counseling and prena‐tal diagnosis .