1.Genetic analysis of a fetus pedigree affected with Thyroid dyshormonogenesis type 5 combined with familial Neurofibromatosis type 1.
Bingbo ZHOU ; Chuan ZHANG ; Xiaojuan LIN ; Lei ZHENG ; Panpan MA ; Ling HUI
Chinese Journal of Medical Genetics 2025;42(3):300-306
OBJECTIVE:
To explore the genetic testing outcomes of a fetal family with Thyroid dyshormonogenesis type 5 (TDH5) and familial Neurofibromatosis type 1 (NF1), and to clarify the association between clinical manifestations and genetic variations.
METHODS:
One case of a TDH5 combined with familiar NF1 fetus treated at Gansu Maternal and Child Health Hospital in January 2024 was selected as the research subject. The clinical and family history data of the fetus were collected by retrospective research method. 10-15 mL of fetal amniotic fluid, and 2-3 mL of peripheral blood from the parents, sister, and grandfather of the fetus were collected, and genomic DNA was extracted for trio whole-exome sequencing (trio-WES). The Sanger sequencing was utilized to validate candidate variants for family verification. According to the Standards and Guidelines for the Interpretation and Reporting of Sequence Variants of the American Society of Medical Genetics and Genomics (ACMG) (hereafter referred to as the ACMG guidelines), the pathogenicity of the detected variants was classified. This study has been approved by the Medical Ethics Committee of Gansu Maternal and Child Health Hospital [Ethics No.(2021)GSFY(65)].
RESULTS:
The fetal ultrasound indicated the nuchal translucency (NT) thickening, and the thyroid function test results of the sister showed an increase in thyroid stimulating hormone and a decrease in free thyroid hormone. Simultaneously, there were cafe-au-lait macules of various sizes in multiple parts of the body of the sister, and the mother had a similar cafe-au-lait macules phenotype. The trio-WES results revealed that there was a c.413dupA (p.Tyr138*) frameshift mutation in exon4 and c.573G>A (p.Trp191*) nonsense mutation in exon5 of the fetal DUOXA2, which were inherited from the mother and father, respectively. In accordance with the ACMG guidelines, they were classified as pathogenic variant (PVS1+PM2_Supporting+PM3) and likely pathogenic variant (PVS1+PM2_Supporting), respectively. And the nonsense mutation c.6972C>A (p.Tyr2264*) was detected in exon46 of the NF1 in the fetus, inherited from the mother maternal grandfather. The genetic testing results of the first sister and proband in this case were consistent, and the DUOXA2 and NF1 of the second sister were both wild-type. According to the ACMG guidelines, c.6972C>A (p.Tyr2264 *) was classified as pathogenic variant (PVS1+PS4_Supporting+PP4+PM2_Supporting).
CONCLUSION
The mutations in the DUOXA2 gene c.413dupA (p.Tyr138*) and c.573G>A (p.Trp191*), and the NF1 gene c.6972C>A (p.Tyr2264*) might be the genetic causes of TDH5 combined with familiar NF1 in proband. The discovery of the DUOXA2 gene c.573G>A (p.Trp191*) enriches the spectrum of pathogenic gene variations.
Humans
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Female
;
Pedigree
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Pregnancy
;
Neurofibromatosis 1/complications*
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Male
;
Genetic Testing
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Adult
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Thyroid Dysgenesis/genetics*
;
Fetus
;
Exome Sequencing
;
Mutation
2.Correlation and predictive value analysis of serum miR-34b and miR-181c levels with the prognosis of elderly AIS patients with mechanical thrombectomy
Lei ZHAO ; Shuang TANG ; Xiaojuan JING
International Journal of Laboratory Medicine 2025;46(10):1206-1211
Objective To analyze the correlation and predictive value of serum microRNA(miR)-34b and miR-181c levels with the prognosis of elderly acute ischemic stroke(AIS)patients with mechanical thrombec-tomy.Methods A total of 180 elderly AIS patients in Suining Central Hospital from January 2023 to January 2024 were selected as the study group.According to the 2∶1 control principle,90 healthy elderly patients at the same age and during the same period were selected as the control group.The general data and serum miR-34b and miR-181c levels in the two groups were compared,and the serum miR-34b and miR-181c levels of pa-tients with different degrees of neurological impairment in the study group were compared,and the correlation between the levels of serum miR-34b and miR-181c and the degree of neurological impairment in elderly AIS patients was analyzed.General data and serum miR-34b and miR-181c levels of patients with different progno-sis were compared at admission,and factors affecting adverse prognosis were analyzed,as well as the value of serum miR-34b and miR-181c in predicting adverse prognosis.Results The serum miR-34b level in the study group was lower than that in the control group,and the serum miR-181c level was higher than that in the con-trol group(P<0.05).In the study group,the serum miR-34b level of patients with severe neurological im-pairment was lower than that of moderate and mild patients,the level of miR-181c was higher than that of moderate and mild patients,and the level of miR-181c was higher than that of mild patients(P<0.05).The serum miR-34b levels in patients with severe neurological impairment in the study group were lower than those in moderate and mild patients at admission,and those in moderate patients were lower than those in mild patients,miR-181c levels were higher than those in moderate and mild patients,and moderate patients were higher than those in mild patients(P<0.05).The level of serum miR-34b was negatively correlated with the degree of neurological impairment,and the level of miR-181c was positively correlated with the degree of neu-rological impairment(P<0.05).The proportion of diabetes mellitus,National Institutes of Health Stroke Scale(NIHSS)score at admission,time from onset to treatment and serum miR-181c level in patients with poor prognosis were higher than those with good prognosis,and the level of miR-34b was lower than those with good prognosis(P<0.05).Diabetes mellitus,time from onset to treatment,NIHSS score at admission,and serum miR-181c level were all independent risk factors for poor prognosis in elderly AIS patients with me-chanical thrombectomy,while serum miR-34b level was an independent protective factor(P<0.05).The area under the curve(AUC)of serum miR-34b and miR-181c were 0.751 and 0.758 respectively in predicting the poor prognosis,and the AUC of combined miR-34B and miR-181c was 0.867,which was greater than the AUC predicted by alone(P<0.05).Conclusion The levels of serum miR-34b and miR-181c are the factors affect-ing the poor prognosis of elderly AIS patients with mechanical thrombectomy,and have the predictive value for the prognosis.
3.The impact of spontaneous portosystemic shunt on clinical outcomes in patients with liver cirrhosis and hepatic encephalopathy
Qiao KE ; Ting LIN ; Xiaojuan LEI ; Xiadi WENG ; Jian HE ; Xinhui HUANG ; Ling LI ; Wuhua GUO
Chinese Journal of Hepatology 2025;33(5):440-447
Objective:To investigate the incidence, clinical characteristics, and impact of spontaneous portosystemic shunt (SPSS) in patients with liver cirrhosis combined with hepatic encephalopathy (HE).Methods:The basic clinical and follow-up data were retrospectively analyzed for patients diagnosed with cirrhosis combined with HE at Mengchao Hepatobiliary Hospital of Fujian Medical University from January 2017 to December 2022. The patients were divided into large and small SPSS groups and a control group based on the results of abdominal enhanced CT or MRI.The clinical characteristics and outcome differences were compared among the three groups. Kaplan-Meier survival curves were used to compare HE-free survival time and overall survival time among the three groups. The log-rank test was used to compare the differences between groups. Cox regression analysis was used to identify the relevant risk factors affecting HE-free survival time and overall survival time.Results:A total of 223 cases with liver cirrhosis combined with HE were enrolled, including 150 in the SPSS and 73 in the control groups. The incidence rate of SPSS was 67.3% (150/223). The group was divided into small SPSS (79/150, 52.7%) and large SPSS group (71/150, 47.3%) according to the cross-sectional area of the diversion channel. The HE-free survival was shorter in the small and large SPSS groups compared with the control group (35.5 months in the small SPSS group and 21.3 months in the large SPSS group; P<0.001). The HE-free survival time was shorter in the large SPSS than with small SPSS group ( P=0.003). The overall survival time in the small SPSS group and the large SPSS group was shorter compared with the control group (small SPSS group: 39.4 months, large SPSS group: 52.9 months; P<0.001). There was no statistically significant difference in overall survival time between the small SPSS and large SPSS groups ( P=0.700). Cox regression analysis showed that SPSS was an independent risk factor affecting patients' HE-free survival time and overall survival time ( P<0.05). Conclusion:SPSS is more common in patients with liver cirrhosis combined with HE. Patients who combined with SPSS showed significant reductions in both HE-free survival time and overall survival time, especially evident in those with combined large SPSS.
4.Genetic analysis of a fetus pedigree affected with Thyroid dyshormonogenesis type 5 combined with familial Neurofibromatosis type 1
Bingbo ZHOU ; Chuan ZHANG ; Xiaojuan LIN ; Lei ZHENG ; Panpan MA ; Ling HUI
Chinese Journal of Medical Genetics 2025;42(3):300-306
Objective:To explore the genetic testing outcomes of a fetal family with Thyroid secretion disorder type 5 (TDH5) and familial Neurofibromatosis type 1 (NF1), and to clarify the association between clinical manifestations and genetic variations.Methods:One case of a TDH5 combined with familiar NF1 fetus treated at Gansu Maternal and Child Health Hospital in January 2024 was selected as the research subject. The clinical and family history data of the fetus were collected by retrospective research method. 10-15 mL of fetal amniotic fluid, and 2-3 mL of peripheral blood from the parents, sister, and grandfather of the fetus were collected, and genomic DNA was extracted for trio whole-exome sequencing (trio-WES). The Sanger sequencing was utilized to validate candidate variants for family verification. According to the Standards and Guidelines for the Interpretation and Reporting of Sequence Variants of the American Society of Medical Genetics and Genomics (ACMG) (hereafter referred to as the ACMG guidelines), the pathogenicity of the detected variants was classified. This study has been approved by the Medical Ethics Committee of Gansu Maternal and Child Health Hospital [Ethics No.(2021)GSFY(65)].Results:The fetal ultrasound indicated the nuchal translucency (NT) thickening, and the thyroid function test results of the sister showed an increase in thyroid stimulating hormone and a decrease in free thyroid hormone. Simultaneously, there were cafe-au-lait macules of various sizes in multiple parts of the body of the sister, and the mother had a similar cafe-au-lait macules phenotype. The trio-WES results revealed that there was a c. 413dupA(p.Tyr138*) frameshift mutation in exon 4 and c. 573G>A(p.Trp191*) nonsense mutation in exon 5 of the fetal DUOXA2, which were inherited from the mother and father, respectively. In accordance with the ACMG guidelines, they were classified as pathogenic variant (PVS1+ PM2_Supporting+ PM3) and likely pathogenic variant (PVS1+ PM2_Supporting), respectively. And the nonsense mutation c. 6972C>A(p.Tyr2264*) was detected in exon 46 of the NF1 in the fetus, inherited from the mother. The genetic testing results of the first sister and proband in this case were consistent, and the DUOXA2 and NF1 of the second sister were both wild-type. According to the ACMG guidelines, c.6972C>A(p.Tyr2264*) was classified as pathogenic variant (PVS1+ PS4_Supporting+ PP4+ PM2_Supporting). Conclusion:The mutations in the DUOXA2 gene c. 413dupA(p.Tyr138*) and c. 573G>A(p.Trp191*), and the NF1 gene c. 6972C>A(p.Tyr2264*) might be the genetic causes of TDH5 combined with familiar NF1 in proband. The discovery of the DUOXA2 gene c. 573G>A(p.Trp191*) enriches the spectrum of pathogenic gene variations.
5.Risk Factors for Recurrence and Their Predictive Value in Endometriosis Patients After Laparoscopic Surgery
Xiaojuan KONG ; Zhenyu TAN ; Lei LEI
Journal of Sichuan University (Medical Sciences) 2025;56(3):846-851
Objective To identify the factors influencing postoperative recurrence in endometriosis patients after laparoscopic surgery and to evaluate their clinical predictive performance for postoperative recurrence.Methods The clinical data of 190 endometriosis patients who underwent laparoscopic surgery at our hospital between January 2019 and January 2024 were retrospectively collected.Patients were divided into a non-recurrence group(109 cases)and a recurrence group(81 cases)based on their status of postoperative recurrence.Univariate analysis was performed with the clinical data.Multivariate logistic regression analysis was performed to identify the influencing factors of recurrence after laparoscopic surgery.Receiver operating characteristic(ROC)curve analysis was used to evaluate the predictive value of the relevant indicators.Results According to the results of the univariate analysis,the prevalence of preoperative history of dysmenorrhea,number of preoperative pregnancies,history of previous uterine cavity procedures,smoking,and drinking in the non-recurrence group was lower than that in the recurrence group(P<0.05).The non-recurrence group also had lower preoperative serum levels of transforming growth factor-β1(TGF-β1),interleukin(IL)-1β,IL-17,and IL-22 compared with those of the recurrence group(P<0.05).Except for the history of previous uterine cavity procedures,drinking,and the level of IL-17,all other factors were independent risk factors for recurrence after laparoscopic surgery(P<0.05).The area under the curve(AUC)for preoperative serum TGF-β1+IL-1β and TGF-β1+IL-1β+IL-22 was 0.980(95%CI,0.965-0.994)and 0.982(95%CI,0.968-0.996),respectively,indicating a high predictive value for recurrence in patients after laparoscopic surgery.Conclusion The history of preoperative dysmenorrhea,number of preoperative pregnancies,smoking,and preoperative levels of serum TGF-β1,IL-1β,and IL-22 are risk factors for the recurrence of endometriosis after laparoscopic surgery.The combination of TGF-β1 and IL-1β,as well as the combination of TGF-β1,IL-1β,and IL-22,both demonstrated good performance for predicting the recurrence of endometriosis after laparoscopic surgery.
6.Evaluation of surgical efficacy in patients with hepatic cystic echinococcosis in Gansu Province from 2006 to 2023
Xixi CHENG ; Yu FENG ; Xu WANG ; Zhiyi WANG ; Jiaxi LEI ; Mingzhe JIANG ; Guobing YANG ; Xiaojuan ZHANG ; Shijie YANG ; Liying WANG
Chinese Journal of Schistosomiasis Control 2025;37(3):247-254
Objective To evaluate the therapeutic efficacy for surgical treatments among patients with hepatic cystic echinococcosis in Gansu Province from 2006 to 2023, so as to provide insights into optimization of the diagnosis and treatment strategies against hepatic cystic echinococcosis. Methods The demographic and clinical data of all echinococcosis cases included in central government fiscal transfer payment program for echinococcosis control and undergoing surgical treatments in Gansu Province from 2006 to 2023 were captured. Hepatic cystic echinococcosis patients with complete medical records and follow-up data were included in the study, and patients’ characteristics, including hospital where patients received diagnosis and treatment, methods of case identification, year of surgery, classification of lesions, number of lesions, size of lesions, course of disease, surgical methods, and post-surgical follow-up data. The cure and recurrence of hepatic cystic echinococcosis were evaluated according to the Guidelines for Management of Echinococcosis Patients in the Central Government Fiscal Transfer Payment Program, and the cure and recurrent rates were calculated. Results Data were collected from 1 686 surgical patients with hepatic cystic echinococcosis. According to the inclusion and exclusion criteria, 1 222 hepatic cystic echinococcosis patients undergoing surgical treatments were included during the period from 2006 to 2022, including 1 166 cured patients (95.42%) and 88 patients with postsurgical recurrence (7.20%), and the cure rate of surgical treatments appeared a tendency towards a rise among patients with hepatic cystic echinococcosis from 2008 to 2022 (χ2trend = 19.39, P < 0.05). The cure rates of hepatic cystic echinococcosis were 100% (177/177), 94.81% (128/135) and 94.62% (861/910) among patients detected through regular physical examinations, screened by the central government fiscal transfer payment program for echinococcosis control, and those who passively sought healthcare services, respectively (χ2 = 9.95, P < 0.05). The cure rates of hepatic cystic echinococcosis were 95.96% (1 046/1 090) among patients with a disease course of 2 years and less and 90.90% (120/132) among patients with a disease course of over 2 years (χ2 = 6.87, P < 0.05), and there were significant differences in the cure rates among patients with hepatic cystic echinococcosis in terms of number of lesions (χ2 = 24.44, P < 0.05) and surgical methods (P < 0.05). The cure rate of hepatic cystic echinococcosis patients was significantly higher following initiation of the central government fiscal transfer payment program for echinococcosis control (96.06%, 1 096/1 141) than before the program (86.42%, 70/81) (χ2 = 16.06, P < 0.05), and the cure rate of hepatic cystic echinococcosis patients was significantly higher in designated hospitals (96.48%, 741/768) than in non-designated hospitals (93.37%, 366/392) (χ2 = 5.78, P < 0.05). The median follow-up period was 4 (interquartile range, 7) years among 1 222 hepatic cystic echinococcosis patients undergoing surgical treatments. The recurrent rate of hepatic cystic echinococcosis appeared a tendency towards a decline from 2008 to 2022 (χ2trend = 36.86, P < 0.05), with a reduction from 23.08% (9/39) in 2008 to 1.85% (1/54) in 2021, and the post-surgical recurrence rate of hepatic cystic echinococcosis was lower following initiation of the central government fiscal transfer payment program for echinococcosis control (5.87%, 67 / 1 141) than before the program (25.93%, 21/81) (χ2 = 45.51, P < 0.05). In addition, the post-surgical recurrence rate of hepatic cystic echinococcosis was higher in non-designated hospitals (10.46%, 41/392) than in designated hospitals (5.60%, 43/768) (χ2 = 9.12, P < 0.05), and there was a significant difference in the post-surgical recurrence rate among patients with hepatic cystic echinococcosis in terms of surgical methods (P < 0.05), with the highest recurrence rate (11.54%) seen among patients undergoing percutaneous fine-needle aspiration of cyst fluids-based surgical procedures (P < 0.05). Conclusion Since the initiation of the central government fiscal transfer payment program for echinococcosis control in Gansu Province in 2006, an increase in the surgical cure rate and a reduction in the recurrence of hepatic cystic echinococcosis had been found among patients with hepatic cystic echinococcosis, indicating a high overall therapeutic efficacy.
7.Therapeutic effect of biomimetic electrical stimulation combined with sequential treatment of estrogen and progesterone on premature ovarian failure and its influence on uterine artery hemodynamics
Lei ZHANG ; Yazhi FAN ; Xiaojuan ZHAO
Clinical Medicine of China 2025;41(2):93-98
Objective:To explore the therapeutic effectiveness of using biomimetic electrical stimulation in conjunction with hormone replacement therapy involving estrogen and progesterone sequentially on premature ovarian failure and its influence on uterine artery hemodynamics.Methods:90 patients with premature ovarian failure in the First People's Hospital of Xianyang were selected from December 2022 to December 2023. According to the principle of matching the baseline characteristics between groups, the above patients were divided into observation group (pink ball, 45 cases) and control group (black ball, 45 cases) by random touching pink-black ball. The control group received estrogen-progesterone sequential therapy. In contrast, the observation group added biomimetic electrical stimulation combined therapy on the basis of the control group. The therapeutic effect, sex hormones (follicle stimulating hormone (FSH), luteinizing hormone (LH), estradiol), uterine artery hemodynamics indicators (uterine artery peak systolic velocity (PSV), pulsatility index (PI), resistance index) and occurrence of adverse reactions were compared between groups of patients. Measurement data with normal distribution were expressed as xˉ± s, and independent sample t test was used for between-group comparison of mean data and paired t-test was used for comparison before and after treatment. The percentage of enumeration data was calculated, and between-group rate was compared by chi-square test. P<0.05 was considered statistically significant. Results:Total effective rate with 96.56%(43/45) in observation group was higher than 82.22%(37/45) in control group ( χ2=4.05, P=0.044). After the end of treatment, FSH, LH, PI and resistance index in both groups were decreased, but the above indicators in observation group ((35.12±6.23) U/L, (33.56±4.12) U/L, 1.97±0.59, 0.41±0.13) were lower than those in control group ((49.23±6.87) U/L, (46.25±4.32) U/L, 2.33±1.04, 0.58±0.22), while the estradiol and PSV in both groups were increased, and the two indicators in observation group ((38.23±5.32) ng/L, (19.68±3.25) cm/s) were higher than those in control group were higher than those in control group ((32.12±5.12) ng/L, (16.44±2.03) cm/s) ( t value were 10.21, 2.52, 2.02, 4.62, 5.55, 5.67, respectively; Pvalue were <0.001, 0.014, 0.046, <0.001, <0.001, <0.001, respectively). The adverse reactions in the observation and control groups were nausea and vomiting (3 cases and 4 cases ), headache (2 cases and 4 cases), breast pain (1 case and 3 cases), and abdominal pain (2 cases and 4 cases), respectively,There were no statistical differences in incidence rates of adverse reactions between groups ( χ2 value were 0.16, 0.71, 1.05, and 0.71, respectively; P value were 0.694, 0.398, 0.306, and 0.398, respectively). Conclusion:The combination of biomimetic electrical stimulation technology and sequential therapy of estrogen and progesterone has shown outstanding efficacy in treating premature ovarian failure, promoting the synthesis of sex hormones in patients, improving uterine blood supply, and having high safety.
8.Therapeutic effect of biomimetic electrical stimulation combined with sequential treatment of estrogen and progesterone on premature ovarian failure and its influence on uterine artery hemodynamics
Lei ZHANG ; Yazhi FAN ; Xiaojuan ZHAO
Clinical Medicine of China 2025;41(2):93-98
Objective:To explore the therapeutic effectiveness of using biomimetic electrical stimulation in conjunction with hormone replacement therapy involving estrogen and progesterone sequentially on premature ovarian failure and its influence on uterine artery hemodynamics.Methods:90 patients with premature ovarian failure in the First People's Hospital of Xianyang were selected from December 2022 to December 2023. According to the principle of matching the baseline characteristics between groups, the above patients were divided into observation group (pink ball, 45 cases) and control group (black ball, 45 cases) by random touching pink-black ball. The control group received estrogen-progesterone sequential therapy. In contrast, the observation group added biomimetic electrical stimulation combined therapy on the basis of the control group. The therapeutic effect, sex hormones (follicle stimulating hormone (FSH), luteinizing hormone (LH), estradiol), uterine artery hemodynamics indicators (uterine artery peak systolic velocity (PSV), pulsatility index (PI), resistance index) and occurrence of adverse reactions were compared between groups of patients. Measurement data with normal distribution were expressed as xˉ± s, and independent sample t test was used for between-group comparison of mean data and paired t-test was used for comparison before and after treatment. The percentage of enumeration data was calculated, and between-group rate was compared by chi-square test. P<0.05 was considered statistically significant. Results:Total effective rate with 96.56%(43/45) in observation group was higher than 82.22%(37/45) in control group ( χ2=4.05, P=0.044). After the end of treatment, FSH, LH, PI and resistance index in both groups were decreased, but the above indicators in observation group ((35.12±6.23) U/L, (33.56±4.12) U/L, 1.97±0.59, 0.41±0.13) were lower than those in control group ((49.23±6.87) U/L, (46.25±4.32) U/L, 2.33±1.04, 0.58±0.22), while the estradiol and PSV in both groups were increased, and the two indicators in observation group ((38.23±5.32) ng/L, (19.68±3.25) cm/s) were higher than those in control group were higher than those in control group ((32.12±5.12) ng/L, (16.44±2.03) cm/s) ( t value were 10.21, 2.52, 2.02, 4.62, 5.55, 5.67, respectively; Pvalue were <0.001, 0.014, 0.046, <0.001, <0.001, <0.001, respectively). The adverse reactions in the observation and control groups were nausea and vomiting (3 cases and 4 cases ), headache (2 cases and 4 cases), breast pain (1 case and 3 cases), and abdominal pain (2 cases and 4 cases), respectively,There were no statistical differences in incidence rates of adverse reactions between groups ( χ2 value were 0.16, 0.71, 1.05, and 0.71, respectively; P value were 0.694, 0.398, 0.306, and 0.398, respectively). Conclusion:The combination of biomimetic electrical stimulation technology and sequential therapy of estrogen and progesterone has shown outstanding efficacy in treating premature ovarian failure, promoting the synthesis of sex hormones in patients, improving uterine blood supply, and having high safety.
9.Genetic analysis of a fetus pedigree affected with Thyroid dyshormonogenesis type 5 combined with familial Neurofibromatosis type 1
Bingbo ZHOU ; Chuan ZHANG ; Xiaojuan LIN ; Lei ZHENG ; Panpan MA ; Ling HUI
Chinese Journal of Medical Genetics 2025;42(3):300-306
Objective:To explore the genetic testing outcomes of a fetal family with Thyroid secretion disorder type 5 (TDH5) and familial Neurofibromatosis type 1 (NF1), and to clarify the association between clinical manifestations and genetic variations.Methods:One case of a TDH5 combined with familiar NF1 fetus treated at Gansu Maternal and Child Health Hospital in January 2024 was selected as the research subject. The clinical and family history data of the fetus were collected by retrospective research method. 10-15 mL of fetal amniotic fluid, and 2-3 mL of peripheral blood from the parents, sister, and grandfather of the fetus were collected, and genomic DNA was extracted for trio whole-exome sequencing (trio-WES). The Sanger sequencing was utilized to validate candidate variants for family verification. According to the Standards and Guidelines for the Interpretation and Reporting of Sequence Variants of the American Society of Medical Genetics and Genomics (ACMG) (hereafter referred to as the ACMG guidelines), the pathogenicity of the detected variants was classified. This study has been approved by the Medical Ethics Committee of Gansu Maternal and Child Health Hospital [Ethics No.(2021)GSFY(65)].Results:The fetal ultrasound indicated the nuchal translucency (NT) thickening, and the thyroid function test results of the sister showed an increase in thyroid stimulating hormone and a decrease in free thyroid hormone. Simultaneously, there were cafe-au-lait macules of various sizes in multiple parts of the body of the sister, and the mother had a similar cafe-au-lait macules phenotype. The trio-WES results revealed that there was a c. 413dupA(p.Tyr138*) frameshift mutation in exon 4 and c. 573G>A(p.Trp191*) nonsense mutation in exon 5 of the fetal DUOXA2, which were inherited from the mother and father, respectively. In accordance with the ACMG guidelines, they were classified as pathogenic variant (PVS1+ PM2_Supporting+ PM3) and likely pathogenic variant (PVS1+ PM2_Supporting), respectively. And the nonsense mutation c. 6972C>A(p.Tyr2264*) was detected in exon 46 of the NF1 in the fetus, inherited from the mother. The genetic testing results of the first sister and proband in this case were consistent, and the DUOXA2 and NF1 of the second sister were both wild-type. According to the ACMG guidelines, c.6972C>A(p.Tyr2264*) was classified as pathogenic variant (PVS1+ PS4_Supporting+ PP4+ PM2_Supporting). Conclusion:The mutations in the DUOXA2 gene c. 413dupA(p.Tyr138*) and c. 573G>A(p.Trp191*), and the NF1 gene c. 6972C>A(p.Tyr2264*) might be the genetic causes of TDH5 combined with familiar NF1 in proband. The discovery of the DUOXA2 gene c. 573G>A(p.Trp191*) enriches the spectrum of pathogenic gene variations.
10.The impact of spontaneous portosystemic shunt on clinical outcomes in patients with liver cirrhosis and hepatic encephalopathy
Qiao KE ; Ting LIN ; Xiaojuan LEI ; Xiadi WENG ; Jian HE ; Xinhui HUANG ; Ling LI ; Wuhua GUO
Chinese Journal of Hepatology 2025;33(5):440-447
Objective:To investigate the incidence, clinical characteristics, and impact of spontaneous portosystemic shunt (SPSS) in patients with liver cirrhosis combined with hepatic encephalopathy (HE).Methods:The basic clinical and follow-up data were retrospectively analyzed for patients diagnosed with cirrhosis combined with HE at Mengchao Hepatobiliary Hospital of Fujian Medical University from January 2017 to December 2022. The patients were divided into large and small SPSS groups and a control group based on the results of abdominal enhanced CT or MRI.The clinical characteristics and outcome differences were compared among the three groups. Kaplan-Meier survival curves were used to compare HE-free survival time and overall survival time among the three groups. The log-rank test was used to compare the differences between groups. Cox regression analysis was used to identify the relevant risk factors affecting HE-free survival time and overall survival time.Results:A total of 223 cases with liver cirrhosis combined with HE were enrolled, including 150 in the SPSS and 73 in the control groups. The incidence rate of SPSS was 67.3% (150/223). The group was divided into small SPSS (79/150, 52.7%) and large SPSS group (71/150, 47.3%) according to the cross-sectional area of the diversion channel. The HE-free survival was shorter in the small and large SPSS groups compared with the control group (35.5 months in the small SPSS group and 21.3 months in the large SPSS group; P<0.001). The HE-free survival time was shorter in the large SPSS than with small SPSS group ( P=0.003). The overall survival time in the small SPSS group and the large SPSS group was shorter compared with the control group (small SPSS group: 39.4 months, large SPSS group: 52.9 months; P<0.001). There was no statistically significant difference in overall survival time between the small SPSS and large SPSS groups ( P=0.700). Cox regression analysis showed that SPSS was an independent risk factor affecting patients' HE-free survival time and overall survival time ( P<0.05). Conclusion:SPSS is more common in patients with liver cirrhosis combined with HE. Patients who combined with SPSS showed significant reductions in both HE-free survival time and overall survival time, especially evident in those with combined large SPSS.

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