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 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 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 This study aimed to analyze the current epidemic situation of cancer in Yunnan province in 2020,and to provide theoretical basis for the prevention and treatment of cancer in Yunnan province.Methods The data on the incidence and mortality of cancer were collected from 129 cancer registration areas in Yunnan province in 2020.A total of 89 counties(cities,dis-tricts)that met the quality control standards were included in this analysis.Among them,there were 16 in urban areas,covering a pop-ulation of 7,593,622(24.16%),and 73 in rural areas,covering a population of 23,838,542(75.84%).The number of malignant tumor cases,deaths,the crude incidence and China age-standardized incidence(China Standardized Incidence),the crude mortality and China age-standardized mortality(China Standardized Mortality),the cumulative incidence and mortality from 0 to 74 years old,as well as the order of cancer incidence and death were statistical analyzed.Results In 2020,66,719 new cases of cancer were re-ported from 89 tumor registration areas in Yunnan province,with a crude rate of 212.26/100,000 and the China age-standardized in-cidence of 150.33/100,000;The reported number of deaths from cancer was 39,251,with a crude mortality of 124.88/100,000 and the China age-standardized mortality of 82.45/100,000.The incidence and mortality of cancer were higher in men than those in fe-male,and higher in rural than those in urban areas.According to the crude incidence rate and crude mortality,the top 5 cancers with the highest crude incidence were lung cancer,female breast cancer,colo-rectum cancer,liver cancer and thyroid cancer,and the top 5 cancers with the highest crude mortality were lung cancer,liver cancer,colo-rectum cancer,stomach cancer and female breast cancer.Conclusion Lung cancer,liver cancer,colo-rectum cancer and female breast cancer are still the key cancers for prevention and con-trol in Yunnan province.The incidence of thyroid cancer is relatively high,and there are significant differences in the incidence and mortality of cancer between urban and rural areas and between sexes.The corresponding cancer prevention should be carried out ac-cording to the current epidemic situation of cancer in Yunnan province.

Objective The aim of this study was to analyze the incidence and mortality of prostate cancer in cancer registra-tion areas of Yunnan province in 2020,as well as its changing trends from 2012 to 2020,and provide suggestions for the prevention and treatment of prostate cancer in Yunnan province.Methods The data of prostate cancer incidence and mortality in cancer regis-tration areas of Yunnan province from 2012 to 2020 were collected and organized.Excel 2016 and SPSS 18.0 software were used to calculate the crude incidence,crude mortality,age-standardized incidence rate by World standard population(ASIRW),age-stand-ardized mortality rate by Chinese standard population(ASMRC),truncated rate,cumulative rate and other indicators.ASIRW and ASMRC were calculated by using Segi's World population composition.Joinpoint 4.8.0.1 software was used to calculate the annual percentage change(APC)and 95%CI of ASIRW and ASMRC of prostate cancer from 2012 to 2020,and analyze their annual change trends.Results In 2020,the crude incidence and ASIRW of male prostate cancer in cancer registration areas of Yunnan province were 9.71/100,000 and 6.21/100,000,respectively.ASIRW in urban areas(7.94/100,000)was higher than that in rural areas(5.48/100,000).In 2020,the crude mortality and ASMRC of male prostate cancer in cancer registration areas of Yunnan province were 4.68/100,000 and 2.87/100,000,respectively.ASMRC in urban areas(3.68/100,000)was higher than that in rural areas(2.53/100,000).In 2020,the incidence and mortality of male prostate cancer in Yunnan province increased with age,were at a low level before the age of 45,and began to rise rapidly after the age of 55.From 2012 to 2020,there was no statistically significant change trend in ASIRW and ASMRC of male prostate cancer in Yunnan province(APC were 1.79%and 3.61%,P>0.05).However,ASIRW and ASMRC of rural males were on the rise(APC were 4.45%and 3.85%,respectively,P<0.05).Conclusion ASIRW and ASMRC of male prostate cancer in cancer registration areas of Yunnan province in 2020 are higher in urban men than those in rural areas.The change trend of ASIRW and ASMRC from 2012 to 2020 is flat,and rural elderly men should be paid more attention.

Objective This study aimed to analyze the incidence and mortality of cervical cancer in tumor registration areas of Yunnan province in 2020,as well as the trend of incidence and mortality from 2012 to 2020,in order to provide a basis for the pre-vention and treatment of cervical cancer in Yunnan province.Methods The data of cervical cancer incidence and mortality were col-lected and sorted out in tumor registration areas of Yunnan province from 2012 to 2020.The crude incidence,crude mortality,age-standardized incidence rate by World standard population(ASIRW)(referred to the World standard incidence),age-standardized mortality rate by World standard population(ASMRW)(referred to the World standard mortality)and other indicators of cervical canc-er in 2020 were statistically analyzed according to the urban and rural areas.The annual percent change(APC)was used to evaluate the changing trend of cervical cancer incidence and mortality from 2012 to 2020,and the GM(1,1)model was used to predict the crude incidence and ASIRW from 2021 to 2025.Results In 2020,there were 2426 new cases of cervical cancer in tumor registration area of Yunnan province,ranking fifth in the incidence of female malignant tumors.The crude incidence and ASIRW were 15.83/100,000 and 11.16/100,000,respectively.There were 831 deaths from cervical cancer,ranking sixth deaths of female malignant tumors.The crude mortality and ASMRW were 5.42/100,000 and 3.52/100,000,respectively.ASIRW was higher in rural areas(11.86/100,000)than that in urban areas(9.11/100,000).ASMRW was slightly higher in urban areas(3.63/100,000)than that in rural areas(3.48/100,000).The age-specific incidence of cervical cancer increased rapidly after the age of 20,and reached a peak in the 55-59 age group;The age-specific mortality of cervical cancer increased rapidly after the age of 35,reaching a peak in the 75-79 age group.ASIRW of cervical cancer in Yunnan province from 2012 to 2020 showed a downward trend with annual changes(APC=-7.54%,95%CI:-13.19%--1.53%),and the trend change was statistically significant(P<0.05).The prediction of the GM(1,1)model showed that the crude incidence and ASIRW of cervical cancer in Yunnan province would continue to decline from 2021 to 2025.Conclusion The incidence and mortality of cervical cancer are relatively low in Yunnan province,but it is still a common malignant tumor in women.The incidence of cervical cancer in Yunnan province is showing a trend of becoming younger,and rural women are the key population for prevention and treatment.

Objective This study aimed to analyze the current epidemic situation of cancer in Yunnan province in 2020,and to provide theoretical basis for the prevention and treatment of cancer in Yunnan province.Methods The data on the incidence and mortality of cancer were collected from 129 cancer registration areas in Yunnan province in 2020.A total of 89 counties(cities,dis-tricts)that met the quality control standards were included in this analysis.Among them,there were 16 in urban areas,covering a pop-ulation of 7,593,622(24.16%),and 73 in rural areas,covering a population of 23,838,542(75.84%).The number of malignant tumor cases,deaths,the crude incidence and China age-standardized incidence(China Standardized Incidence),the crude mortality and China age-standardized mortality(China Standardized Mortality),the cumulative incidence and mortality from 0 to 74 years old,as well as the order of cancer incidence and death were statistical analyzed.Results In 2020,66,719 new cases of cancer were re-ported from 89 tumor registration areas in Yunnan province,with a crude rate of 212.26/100,000 and the China age-standardized in-cidence of 150.33/100,000;The reported number of deaths from cancer was 39,251,with a crude mortality of 124.88/100,000 and the China age-standardized mortality of 82.45/100,000.The incidence and mortality of cancer were higher in men than those in fe-male,and higher in rural than those in urban areas.According to the crude incidence rate and crude mortality,the top 5 cancers with the highest crude incidence were lung cancer,female breast cancer,colo-rectum cancer,liver cancer and thyroid cancer,and the top 5 cancers with the highest crude mortality were lung cancer,liver cancer,colo-rectum cancer,stomach cancer and female breast cancer.Conclusion Lung cancer,liver cancer,colo-rectum cancer and female breast cancer are still the key cancers for prevention and con-trol in Yunnan province.The incidence of thyroid cancer is relatively high,and there are significant differences in the incidence and mortality of cancer between urban and rural areas and between sexes.The corresponding cancer prevention should be carried out ac-cording to the current epidemic situation of cancer in Yunnan province.

Objective The aim of this study was to analyze the incidence and mortality of prostate cancer in cancer registra-tion areas of Yunnan province in 2020,as well as its changing trends from 2012 to 2020,and provide suggestions for the prevention and treatment of prostate cancer in Yunnan province.Methods The data of prostate cancer incidence and mortality in cancer regis-tration areas of Yunnan province from 2012 to 2020 were collected and organized.Excel 2016 and SPSS 18.0 software were used to calculate the crude incidence,crude mortality,age-standardized incidence rate by World standard population(ASIRW),age-stand-ardized mortality rate by Chinese standard population(ASMRC),truncated rate,cumulative rate and other indicators.ASIRW and ASMRC were calculated by using Segi's World population composition.Joinpoint 4.8.0.1 software was used to calculate the annual percentage change(APC)and 95%CI of ASIRW and ASMRC of prostate cancer from 2012 to 2020,and analyze their annual change trends.Results In 2020,the crude incidence and ASIRW of male prostate cancer in cancer registration areas of Yunnan province were 9.71/100,000 and 6.21/100,000,respectively.ASIRW in urban areas(7.94/100,000)was higher than that in rural areas(5.48/100,000).In 2020,the crude mortality and ASMRC of male prostate cancer in cancer registration areas of Yunnan province were 4.68/100,000 and 2.87/100,000,respectively.ASMRC in urban areas(3.68/100,000)was higher than that in rural areas(2.53/100,000).In 2020,the incidence and mortality of male prostate cancer in Yunnan province increased with age,were at a low level before the age of 45,and began to rise rapidly after the age of 55.From 2012 to 2020,there was no statistically significant change trend in ASIRW and ASMRC of male prostate cancer in Yunnan province(APC were 1.79%and 3.61%,P>0.05).However,ASIRW and ASMRC of rural males were on the rise(APC were 4.45%and 3.85%,respectively,P<0.05).Conclusion ASIRW and ASMRC of male prostate cancer in cancer registration areas of Yunnan province in 2020 are higher in urban men than those in rural areas.The change trend of ASIRW and ASMRC from 2012 to 2020 is flat,and rural elderly men should be paid more attention.

Objective This study aimed to analyze the incidence and mortality of cervical cancer in tumor registration areas of Yunnan province in 2020,as well as the trend of incidence and mortality from 2012 to 2020,in order to provide a basis for the pre-vention and treatment of cervical cancer in Yunnan province.Methods The data of cervical cancer incidence and mortality were col-lected and sorted out in tumor registration areas of Yunnan province from 2012 to 2020.The crude incidence,crude mortality,age-standardized incidence rate by World standard population(ASIRW)(referred to the World standard incidence),age-standardized mortality rate by World standard population(ASMRW)(referred to the World standard mortality)and other indicators of cervical canc-er in 2020 were statistically analyzed according to the urban and rural areas.The annual percent change(APC)was used to evaluate the changing trend of cervical cancer incidence and mortality from 2012 to 2020,and the GM(1,1)model was used to predict the crude incidence and ASIRW from 2021 to 2025.Results In 2020,there were 2426 new cases of cervical cancer in tumor registration area of Yunnan province,ranking fifth in the incidence of female malignant tumors.The crude incidence and ASIRW were 15.83/100,000 and 11.16/100,000,respectively.There were 831 deaths from cervical cancer,ranking sixth deaths of female malignant tumors.The crude mortality and ASMRW were 5.42/100,000 and 3.52/100,000,respectively.ASIRW was higher in rural areas(11.86/100,000)than that in urban areas(9.11/100,000).ASMRW was slightly higher in urban areas(3.63/100,000)than that in rural areas(3.48/100,000).The age-specific incidence of cervical cancer increased rapidly after the age of 20,and reached a peak in the 55-59 age group;The age-specific mortality of cervical cancer increased rapidly after the age of 35,reaching a peak in the 75-79 age group.ASIRW of cervical cancer in Yunnan province from 2012 to 2020 showed a downward trend with annual changes(APC=-7.54%,95%CI:-13.19%--1.53%),and the trend change was statistically significant(P<0.05).The prediction of the GM(1,1)model showed that the crude incidence and ASIRW of cervical cancer in Yunnan province would continue to decline from 2021 to 2025.Conclusion The incidence and mortality of cervical cancer are relatively low in Yunnan province,but it is still a common malignant tumor in women.The incidence of cervical cancer in Yunnan province is showing a trend of becoming younger,and rural women are the key population for prevention and treatment.

Purpose: Invasive ductal carcinoma (IDC) accounts for 90% of triple-negative breast cancer (TNBC). IDC is mainly derived from the breast ductal epithelium which is innervated by the 4th to 6th thoracic sympathetic nerves. However, little is known about the contribution of the interactions between sympathetic nerves and breast cancer cells to the malignant progression of TNBC. Methods: The expression levels of the β2 -adrenergic receptor (β2 -AR, encoded by ADRB2 gene), nerve growth factor (NGF), and tropomyosin receptor kinase A (TrkA) were determined using immunohistochemistry (IHC). NGF expression levels in the serum were compared by enzyme-linked immunosorbent assay (ELISA). Cell proliferation was assessed using the Cell Counting Kit-8 assay. The β2 -AR, NGF, p-ERK, and p-CERB expression levels were determined using western blotting. TNBC cells and neuronal cells of the dorsal root ganglion (DRG) in 2-day-old Sprague Dawley rats were co-cultured. Using norepinephrine (NE), NGF, and β2 -AR, NGF/TrkA blocker pretreatments, the axon growth of each group of DRG neuron cells was detected by immunofluorescence analysis. Results: The sympathetic adrenergic neurotransmitter NE activated the ERK signaling pathway in TNBC cells. NE/β2 -AR signaling promotes NGF secretion. NGF further facilitates the malignant progression of TNBC by increasing sympathetic neurogenesis. In the coculture assay, the sympathetic adrenergic NE/β2 -AR signal pathway also enhanced NGF secretion. NGF binds TrkA in DRG neurons and promotes axonal growth. Conclusion These results suggest that NE/β2 -AR pathway promotes cell proliferation and NGF production in triple-negative breast cancer.