OBJECTIVE: To elucidate the clinical and genetic characteristics of familial cases with Glucose transporter type 1 deficiency syndrome (Glut1DS). METHODS: A survey of family history was conducted on children (proband) with Glut1DS who had visited Peking University First Hospital between November 2008 and April 2024 by focusing on the clinical manifestations of family members. Peripheral venous blood (2 mL) was collected from the pediatric patients and their parents. Genomic DNA was extracted and sequenced subsequently. Sanger sequencing was performed to validate the identified variant sites of the SLC2A1 gene in the probands and their family members. The pathogenicity of suspected variants was analyzed according to the 2015 American College of Medical Genetics and Genomics (ACMG) Standards and Guidelines for the Interpretation of Sequence Variants. The clinical features, auxiliary examinations, and mutational characteristics of family members with SLC2A1 variants were analyzed. This study has been approved by the Clinical Research Ethics Committee of Peking University First Hospital (Ethics No. 2021 Research 332). RESULTS: Among 87 cases with Glut1DS, 10 families with autosomal dominate inherited cases were identified, accounting for 11.0% of the cases. Of the 11 children, 8 were boys and 3 were girls. The onset of the disease had ranged from 3 months to 120 months (median 6 months), with 4 cases of early-onset classic type, 2 cases of late-onset classic type, and 5 cases of non-classic type. Six children had seizures, and 7 exhibited movement disorders. Seven children underwent developmental assessment, of which 3 had mild developmental delay, 2 were borderline, and 2 were normal. Nine children underwent lumbar puncture. The cerebrospinal fluid glucose levels ranged from 1.45 to 2.25 mmol/L (median 1.86 mmol/L), and the cerebrospinal fluid to blood glucose ratios ranged from 0.29 to 0.44 (median 0.35). Among the 8 fathers with SLC2A1 gene variants, 4 were asymptomatic, 2 developed paroxysmal exercise-induced movement disorders (PED) in childhood and adulthood, respectively. 1 had poor memory since childhood, 1 developed migraines during adolescence, and his sister was an asymptomatic carrier. The father with childhood-onset PED had a cerebrospinal fluid test with CSF glucose of 1.85 mmol/L. Of the 3 mothers with SLC2A1 gene mutations, 1 was an asymptomatic carrier; 2 developed PED in childhood and after the age of 20, respectively. The mother who developed PED in childhood also had psychomotor developmental delay. Genetic testing results revealed that among 10 families, 8 carried missense variants, 1 carried a nonsense variant, and 1 carried a small fragment insertion leading to a frameshift variant. Among the 11 cases, SLC2A1 gene variants in 8 children were inherited from their fathers, while in 3 cases, the variants were inherited from their mothers. The pathogenicity of the genetic variants was evaluated according to the Standards and Guidelines for the Interpretation of Sequence Variants published by the ACMG. Among the 8 variants identified in the 10 families, 4 were classified as pathogenic variants, 1 as likely pathogenic, and 3 as variants of uncertain significance (VUS). Four variant sites, including c.204_205insTCTC (p.V69fs), c.412G>C (p.G138R), c.431T>G (p.V144G), and c.875A>G (p.Y292C), were not previously reported in the literature. Among these, the latter three were categorized as VUS. CONCLUSION Familial Glut1DS account for 11.0% of the cases in China, with the majority of SLC2A1 gene variants inherited from the fathers, predominantly missense mutations, and with an autosomal dominant inheritance pattern. Probands tend to have earlier onset and more severe symptoms than their parents, who often present with mild or no symptoms.
Humans ; Male ; Female ; Glucose Transporter Type 1/deficiency* ; Monosaccharide Transport Proteins/deficiency* ; Child ; Child, Preschool ; Carbohydrate Metabolism, Inborn Errors/genetics* ; Mutation ; Infant ; Pedigree ; Adolescent ; Adult

Objective:To review the diagnosis, treatment and quality of life of patients with primary immune thrombocytopenia (ITP) in seven medical centers in some areas of Hubei Province.Methods:A retrospective analysis was conducted on age, disease course, symptoms, diagnosis, and treatment status (including testing items, drug selection, and adverse reactions) of patients with ITP in seven medical centers in Hubei Province from January 2020 to December 2022. An online survey was conducted on the quality of life of patients using the ITP Patient Assessment Questionnaire (ITP-PAQ) .Results:Among the 1033 patients, those with newly diagnosed, persistent, and chronic ITP accounted for 39.8%, 19.1%, and 41.1%, respectively. Most patients exhibit varying degrees of bleeding. Regarding treatment, corticosteroids and thrombopoietin drugs are the most commonly chosen treatment drugs for ITP, and the adverse reactions to treatment mainly include diarrhea, liver dysfunction, and thrombosis. The ITP-PAQ survey of 125 patients revealed that ITP significantly impairs their life quality. Patients with ITP scored significantly lower in fatigue, sleep, fear, exercise, work, and social aspects.Conclusion:A relatively high proportion of patients with ITP progressed to the chronic phase. Corticosteroids and thrombopoietin drugs are the two main treatment drugs for ITP patients. The quality of life of patients with ITP is significantly reduced in multiple dimensions.

Objective:To elucidate the clinical and genetic characteristics of familial cases with Glucose transporter type 1 deficiency syndrome (Glut1DS).Methods:A survey of family history was conducted on children (proband) with Glut1DS who had visited Peking University First Hospital between November 2008 and April 2024 by focusing on the clinical manifestations of family members. Peripheral venous blood (2 mL) was collected from the pediatric patients and their parents. Genomic DNA was extracted and sequenced subsequently. Sanger sequencing was performed to validate the identified variant sites of the SLC2A1 gene in the probands and their family members. The pathogenicity of suspected variants was analyzed according to the 2015 American College of Medical Genetics and Genomics (ACMG) Standards and Guidelines for the Interpretation of Sequence Variants. The clinical features, auxiliary examinations, and mutational characteristics of family members with SLC2A1 variants were analyzed. This study has been approved by the Clinical Research Ethics Committee of Peking University First Hospital (Ethics No. 2021 Research 332). Results:Among 87 cases with Glut1DS, 10 families with autosomal dominate inherited cases were identified, accounting for 11.0% of the cases. Of the 11 children, 8 were boys and 3 were girls. The onset of the disease had ranged from 3 months to 120 months (median 6 months), with 4 cases of early-onset classic type, 2 cases of late-onset classic type, and 5 cases of non-classic type. Six children had seizures, and 7 exhibited movement disorders. Seven children underwent developmental assessment, of which 3 had mild developmental delay, 2 were borderline, and 2 were normal. Nine children underwent lumbar puncture. The cerebrospinal fluid glucose levels ranged from 1.45 to 2.25 mmol/L (median 1.86 mmol/L), and the cerebrospinal fluid to blood glucose ratios ranged from 0.29 to 0.44 (median 0.35). Among the 8 fathers with SLC2A1 gene variants, 4 were asymptomatic, 2 developed paroxysmal exercise-induced movement disorders (PED) in childhood and adulthood, respectively, 1 had poor memory since childhood, 1 developed migraines during adolescence, and his sister was an asymptomatic carrier. The father with childhood-onset PED had a cerebrospinal fluid test with CSF glucose of 1.85 mmol/L. Of the 3 mothers with SLC2A1 gene mutations, 1 was an asymptomatic carrier; 2 developed PED in childhood and after the age of 20 respectively. The mother who developed PED in childhood also had psychomotor developmental delay. Genetic testing results revealed that among 10 families, 8 carried missense variants, 1 carried a nonsense variant, and 1 carried a small fragment insertion leading to a frameshift variant. Among the 11 cases, SLC2A1 gene variants in 8 children were inherited from their fathers, while in 3 cases, the variants were inherited from their mothers. The pathogenicity of the genetic variants was evaluated according to the Standards and Guidelines for the Interpretation of Sequence Variants published by the ACMG. Among the 8 variants identified in the 10 families, 4 were classified as pathogenic variants, 1 as likely pathogenic, and 3 as variants of uncertain significance (VUS). Four variant sites induding, c. 204_205insTCTC (p.V69fs), c. 412G>C (p.G138R), c. 431T>G (p.V144G), and c. 875A>G (p.Y292C), were not previously reported in the literature. Among these, the latter three were categorized as VUS. Conclusion:Familial Glut1DS account for 11.0% of the cases in China, with the majority of SLC2A1 gene variants inherited from the fathers, predominantly missense mutations, and with an autosomal dominant inheritance pattern. Probands tend to have earlier onset and more severe symptoms than their parents, who often present with mild or no symptoms.

Objective:To review the diagnosis, treatment and quality of life of patients with primary immune thrombocytopenia (ITP) in seven medical centers in some areas of Hubei Province.Methods:A retrospective analysis was conducted on age, disease course, symptoms, diagnosis, and treatment status (including testing items, drug selection, and adverse reactions) of patients with ITP in seven medical centers in Hubei Province from January 2020 to December 2022. An online survey was conducted on the quality of life of patients using the ITP Patient Assessment Questionnaire (ITP-PAQ) .Results:Among the 1033 patients, those with newly diagnosed, persistent, and chronic ITP accounted for 39.8%, 19.1%, and 41.1%, respectively. Most patients exhibit varying degrees of bleeding. Regarding treatment, corticosteroids and thrombopoietin drugs are the most commonly chosen treatment drugs for ITP, and the adverse reactions to treatment mainly include diarrhea, liver dysfunction, and thrombosis. The ITP-PAQ survey of 125 patients revealed that ITP significantly impairs their life quality. Patients with ITP scored significantly lower in fatigue, sleep, fear, exercise, work, and social aspects.Conclusion:A relatively high proportion of patients with ITP progressed to the chronic phase. Corticosteroids and thrombopoietin drugs are the two main treatment drugs for ITP patients. The quality of life of patients with ITP is significantly reduced in multiple dimensions.

Objective:To elucidate the clinical and genetic characteristics of familial cases with Glucose transporter type 1 deficiency syndrome (Glut1DS).Methods:A survey of family history was conducted on children (proband) with Glut1DS who had visited Peking University First Hospital between November 2008 and April 2024 by focusing on the clinical manifestations of family members. Peripheral venous blood (2 mL) was collected from the pediatric patients and their parents. Genomic DNA was extracted and sequenced subsequently. Sanger sequencing was performed to validate the identified variant sites of the SLC2A1 gene in the probands and their family members. The pathogenicity of suspected variants was analyzed according to the 2015 American College of Medical Genetics and Genomics (ACMG) Standards and Guidelines for the Interpretation of Sequence Variants. The clinical features, auxiliary examinations, and mutational characteristics of family members with SLC2A1 variants were analyzed. This study has been approved by the Clinical Research Ethics Committee of Peking University First Hospital (Ethics No. 2021 Research 332). Results:Among 87 cases with Glut1DS, 10 families with autosomal dominate inherited cases were identified, accounting for 11.0% of the cases. Of the 11 children, 8 were boys and 3 were girls. The onset of the disease had ranged from 3 months to 120 months (median 6 months), with 4 cases of early-onset classic type, 2 cases of late-onset classic type, and 5 cases of non-classic type. Six children had seizures, and 7 exhibited movement disorders. Seven children underwent developmental assessment, of which 3 had mild developmental delay, 2 were borderline, and 2 were normal. Nine children underwent lumbar puncture. The cerebrospinal fluid glucose levels ranged from 1.45 to 2.25 mmol/L (median 1.86 mmol/L), and the cerebrospinal fluid to blood glucose ratios ranged from 0.29 to 0.44 (median 0.35). Among the 8 fathers with SLC2A1 gene variants, 4 were asymptomatic, 2 developed paroxysmal exercise-induced movement disorders (PED) in childhood and adulthood, respectively, 1 had poor memory since childhood, 1 developed migraines during adolescence, and his sister was an asymptomatic carrier. The father with childhood-onset PED had a cerebrospinal fluid test with CSF glucose of 1.85 mmol/L. Of the 3 mothers with SLC2A1 gene mutations, 1 was an asymptomatic carrier; 2 developed PED in childhood and after the age of 20 respectively. The mother who developed PED in childhood also had psychomotor developmental delay. Genetic testing results revealed that among 10 families, 8 carried missense variants, 1 carried a nonsense variant, and 1 carried a small fragment insertion leading to a frameshift variant. Among the 11 cases, SLC2A1 gene variants in 8 children were inherited from their fathers, while in 3 cases, the variants were inherited from their mothers. The pathogenicity of the genetic variants was evaluated according to the Standards and Guidelines for the Interpretation of Sequence Variants published by the ACMG. Among the 8 variants identified in the 10 families, 4 were classified as pathogenic variants, 1 as likely pathogenic, and 3 as variants of uncertain significance (VUS). Four variant sites induding, c. 204_205insTCTC (p.V69fs), c. 412G>C (p.G138R), c. 431T>G (p.V144G), and c. 875A>G (p.Y292C), were not previously reported in the literature. Among these, the latter three were categorized as VUS. Conclusion:Familial Glut1DS account for 11.0% of the cases in China, with the majority of SLC2A1 gene variants inherited from the fathers, predominantly missense mutations, and with an autosomal dominant inheritance pattern. Probands tend to have earlier onset and more severe symptoms than their parents, who often present with mild or no symptoms.

Heterozygous loss-of-function variants of FOXP4 are associated with neurodevelopmental disorders (NDDs) that exhibit delayed speech development, intellectual disability, and congenital abnormalities. The etiology of NDDs is unclear. Here we found that FOXP4 and N-cadherin are expressed in the nuclei and apical end-feet of radial glial cells (RGCs), respectively, in the mouse neocortex during early gestation. Knockdown or dominant-negative inhibition of Foxp4 abolishes the apical condensation of N-cadherin in RGCs and the integrity of neuroepithelium in the ventricular zone (VZ). Inhibition of Foxp4 leads to impeded radial migration of cortical neurons and ectopic neurogenesis from the proliferating VZ. The ectopic differentiation and deficient migration disappear when N-cadherin is over-expressed in RGCs. The data indicate that Foxp4 is essential for N-cadherin-based adherens junctions, the loss of which leads to periventricular heterotopias. We hypothesize that FOXP4 variant-associated NDDs may be caused by disruption of the adherens junctions and malformation of the cerebral cortex.
Mice ; Animals ; Ependymoglial Cells/physiology* ; Cadherins ; Neurons/metabolism* ; Cerebral Cortex/metabolism* ; Cell Differentiation ; Cell Movement

Objective:To investigate the cognitive level of parents' participation in treatment activities during perioperative period and analyze its influencing factors.Methods:A total of 500 parents of perioperative children treated in Jinan Maternity and Child Care Hospital, Children's Hospital Affiliated to Shandong University and Central Hospital Affiliated to Shandong First Medical University from March to October 2021 were selected by the convenient sampling method. The Cognitive Assessment Scale of Inpatients' Participation in Treatment Activities, Caregiver Positive Perception Scale and Overall Health Literacy Scale were used to investigate the patients. A total of 500 questionnaires were sent out in this study and 487 were effectively received, with an effective recovery of 97.4%.Results:The total cognitive score of 487 perioperative Children's parents' participation in treatment activities was (62.25±7.39) , and the average score of each dimension was from high to low as patients' participation cognition, behavior management cognition and treatment cognition. Multiple linear regression analysis showed that parents' age, educational level, marital status, previous caregiving experience, caregivers' positive feelings, health literacy and hospital stay of children were the factors influencing the cognitive level of parents' participation in treatment activities during perioperative period.Conclusions:Parents' age, education level, marital status, previous nursing experience, positive feelings of caregivers, health literacy and length of hospital stay of children are factors that influence the cognitive level of parents' participation in treatment activities during perioperative period. Targeted intervention measures can be taken in the future to improve the cognitive level of parents' participation in treatment activities during perioperative period to promote the recovery of children.

Objective:To evaluate the role of Toll-like receptor 4 (TLR4) in the mechanism by penehyclidine hydrochloride alleviating lipopolysaccharide (LPS)-induced acute lung injury(ALI)in rats.Methods:Twenty-four healthy male Sprague-Dawley rats, aged 10 weeks, weighing 220-250 g, were divided into 4 groups ( n=6 each) according to the random number table method: normal saline group (NS group), endotoxin-induced ALI group (ALI group), penehyclidine hydrochloride + normal saline group (PHC+ NS group) and penehyclidine hydrochloride + endotoxin-induced ALI group (PHC+ ALI group). ALI was induced by intratracheal instillation of LPS 5 mg/kg in anesthetized animals. In group PHC+ ALI, penehyclidine hydrochloride 2 mg/kg was intraperitoneally injected immediately after intratracheal instillation of LPS. The equal volume of normal saline was injected into the airway in group NS, and penehyclidine hydrochloride 2 mg/kg was intraperitoneally injected immediately after intratracheal instillation of normal saline in group PHC+ NS. The rats were sacrificed at 6 h after intratracheal instillation of LPS or normal saline, and lungs were removed. The lung was lavaged and broncho-alveolar lavage fluid (BALF) was collected for determination of concentrations of tumor necrosis factor-alpha (TNF-α) and interleukin-1beta (IL-1β) by enzyme-linked immunosorbent assay. Lung tissues were obtained for microscopic examination of the pathological changes (with a light microscope) and for determination of wet to dry lung weight ratio (W/D ratio) and TLR4 protein and mRNA expression (by immuno-histochemistry or real-time polymerase chain reaction). Results:Compared with group NS and group PHC+ NS, the W/D ratio and concentrations of TNF-α and IL-1β in BALF were significantly increased, the expression of TLR4 protein and mRNA in lung tissues was up-regulated ( P<0.01), and the pathological changes of lung tissues were aggravated in group ALI . Compared with group ALI, the W/D ratio and concentrations of TNF-α and IL-1β in BALF were significantly decreased, the expression of TLR4 protein and mRNA in lung tissues was down-regulated ( P<0.01), and the pathological changes of lung tissues were significantly mitigated in group PHC+ ALI. Conclusions:The mechanism by which penehyclidine hydrochloride reduces endotoxin-induced lung injury may be related to reduction of TLR4 activity and thus inhibition of pulmonary inflammatory responses in rats.

Objective:To investigate the clinical effect of perforator flap combined with toe transplantation for repairing thumb damage with soft tissue defect of hand.Methods:The retrospective observational study method was used. From May 2014 to June 2019, 8 patients with thumb damage and soft tissue defect of hand were admitted to the 988th Hospital of Joint Logistic Support Force of PLA, including 6 males and 2 females, aged from 25 to 46 years. Among them, thumb damage in 3 cases were degree Ⅱ, 1 case was degree Ⅲ, and 4 cases were degree Ⅳ. All thumb damage were repaired with perforator flap combined with toe transplantation. The skin and soft tissue defects of hand were repaired by free anterolateral thigh perforator flap in 6 cases and free deep inferior epigastric perforator flap in 2 cases. The thumb damage of degree Ⅱ was repaired by the first toe transplantation combined with perforator flap, and thumb damage of degree Ⅲ or Ⅳ was repaired by the second toe transplantation combined with perforator flap. The survival and blood supply of reconstructed thumbs and flaps, and wound healing of donor sites were observed after surgery. All the patients were followed up for 10 to 18 months, the appearance of the reconstructed thumbs, sensory recovery, and foot walking function were observed. At the final follow-up, the functional reconstruction of the thumb was evaluated.Results:All the blood supply and survival of the reconstructed thumbs and flaps were good, and all the wounds of donor sites healed well. During the follow-up, the appearances of the reconstructed thumb and flap were good, the sensation of pain and touch of the finger pulp recovered well, and no significant impact on foot walking function was observed. At the final follow-up, the function of reconstructed thumb was evaluated as excellent in 4 cases, good in 3 cases, and fair in 1 case.Conclusions:The repair method of perforator flap combined with toe transplantation technique can complete the targeted repair of thumb damage with skin and soft tissue defect of hand in one stage, minimizing the foot donor site injury and shortening the course of disease and early rehabilitation, which is one of the ideal methods for the treatment of complex thumb damage.