Objective:To explore the clinical phenotypes and genetic characteristics of a pedigree with Distal arthrogryposis type 5D (DA5D) caused by compound heterozygous variants in the ECEL1 gene. Methods:A child (proband) diagnosed with DA5D and his family members (proband′s parents and sister) who was admitted to the Department of Rehabilitation Medicine of Henan Children′s Hospital in July 2022 due to " multiplex distal arthrogryposis" were enrolled into this study. Clinical data of the proband were collected and peripheral blood samples were obtained from the proband and members of his family about 3 mL. Trio-whole genome sequencing (trio-WGS) was carried out to detected the genetic variations of the proband and his family members. The candidate′s pathogenic gene variants were screened and analyzed by Genome Aggregation Database (gnomAD) and other databases. The screened variants wer annotated for clinical phenotypes using databases like the Online Mendelian Inheritance in Man (OMIM). The pathogenicity of the candidate variants was predicted by bioinformatics tools such as Provean. Based on the guidelines of the American College of Medical Genetics and Genomics (ACMG), pathogenicity ratings were conducted for variant sites. The protein conservation and mutation structure prediction of ECEL1 protein among species were carried out though MEGA-X and PyMOL. The research protocol of this study was reviewed by the Ethics Committee of Henan Provincial Children′s Hospital (Approval No. 2023-H-H01), and informed consent for clinical research was obtained from the guardians of the probands.Results:The proband had multiplex distal arthrogryposis involving hands, feet, knees, and ankles, and had right ptosis, micrognathia, low auricular position, and upturned nose. The parents and sister both had normal phenotypes. Trio-WGS and Sanger sequencing revealed that the child had compound heterozygous variants of paternal c. 1742_c.1743insT and maternal c. 2314T>G, for which the father and sister were carriers of the c. 1742_c.1743insT heterozygous variant and the mother was carrier of c. 2314T>A. Neither mutation site has been reported. According to guidelines of ACMG, the c. 1742_c.1743insT variant was classified as likely pathogenic (PSV1+ PM2_Supporting), and c. 2314T>G was classified as uncertain (PM2_Supporting+ PM3+ PP3). The results of conserved analysis of amino acid residue sequences of ECEL1 protein showed that the missense mutation of the maternal c. 2314T>G(p.Cys772Gly) was highly conserved among humans and other seven species. The protein structure prediction revealed that the c.1742_c.1743insT frameshift mutation led to the protein truncation, and the c. 2314T>G missense mutation resulted in the failure of forming 1 disulfide bond.Conclusion:The compound heterozygous variants of ECEL1 gene were considered to be pathogenic for this DA5D patient, which have expanded the mutational spectrum of the ECEL1 gene and provided a reference for clinical diagnosis as well as genetic counseling for this family.

OBJECTIVE: To explore the clinical phenotypes and genetic characteristics of a pedigree with Distal arthrogryposis type 5D (DA5D) caused by compound heterozygous variants in the ECEL1 gene. METHODS: A child (proband) diagnosed with DA5D and his family members (proband's parents and sister) who was admitted to the Department of Rehabilitation Medicine of Henan Children's Hospital in July 2022 due to "multiplex distal arthrogryposis" were enrolled into this study. Clinical data of the proband were collected and peripheral blood samples were obtained from the proband and members of his family about 3 mL. Trio-whole genome sequencing (trio-WGS) was carried out to detected the genetic variations of the proband and his family members. The candidate's pathogenic gene variants were screened and analyzed by Genome Aggregation Database (gnomAD) and other databases. The screened variants were annotated for clinical phenotypes using databases like the Online Mendelian Inheritance in Man (OMIM). The pathogenicity of the candidate variants was predicted by bioinformatics tools such as Provean. Based on the guidelines of the American College of Medical Genetics and Genomics (ACMG), pathogenicity ratings were conducted for variant sites. The protein conservation and mutation structure prediction of ECEL1 protein among species were carried out though MEGA-X and PyMOL. The research protocol of this study was reviewed by the Ethics Committee of Henan Provincial Children's Hospital (Approval No. 2023-H-H01), and informed consent for clinical research was obtained from the guardians of the probands. RESULTS: The proband had multiplex distal arthrogryposis involving hands, feet, knees, and ankles, and had right ptosis, micrognathia, low auricular position, and upturned nose. The parents and sister both had normal phenotypes. Trio-WGS and Sanger sequencing revealed that the child had compound heterozygous variants of paternal c.1742_c.1743insT and maternal c.2314T>G, for which the father and sister were carriers of the c.1742_c.1743insT heterozygous variant and the mother was carrier of c.2314T>A. Neither mutation site has been reported. According to guidelines of ACMG, the c.1742_c.1743insT variant was classified as likely pathogenic (PSV1+PM2_Supporting), and c.2314T>G was classified as uncertain (PM2_Supporting+PM3+PP3). The results of conserved analysis of amino acid residue sequences of ECEL1 protein showed that the missense mutation of the maternal c.2314T>G (p.Cys772Gly) was highly conserved among humans and other seven species. The protein structure prediction revealed that the c.1742_c.1743insT frameshift mutation led to the protein truncation, and the c.2314T>G missense mutation resulted in the failure of forming 1 disulfide bond. CONCLUSION The compound heterozygous variants of ECEL1 gene were considered to be pathogenic for this DA5D patient, which have expanded the mutational spectrum of the ECEL1 gene and provided a reference for clinical diagnosis as well as genetic counseling for this family.
Humans ; Pedigree ; Arthrogryposis/genetics* ; Male ; Female ; Heterozygote ; Phenotype ; Mutation ; Child ; Metalloendopeptidases

Objective:To summarize the clinical and genetic characteristics of patients with neurodevelopmental disorder with or without variable brain abnormalities (NEDBA) caused by MAPK8IP3 gene variation. Methods:The clinical data and genetic testing results of 2 children with NEDBA treated in Henan Children′s Hospital from August 2019 to January 2022 were collected retrospectively. Literature was searched and reviewed from China National Knowledge Infrastructure, Wanfang Data Knowledge Service Platform, PubMed database and OMIM database (up to October 2024) with" MAPK8IP3 gene ""NEDBA ""neurodevelopmental disorders "as the search terms. The main clinical genetic characteristics of NEDBA caused by MAPK8IP3 gene variation were summarized. Results:The 2 children, a boy aged 1 year and 8 months and a girl aged 1 year and 4 months, both showed global developmental delay and the onset of the disease in infancy. The de novo heterozygous mutation c.1732C>T(p.Arg578Cys) of the MAPK8IP3 gene was detected by whole-exome sequencing. Case 1 was followed up to 3 years and 10 months old, who had severe developmental delay and was accompanied by hip subluxation and strephexopodia. Literature search retrieved 0 Chinese literature and 2 English literatures. A total of 18 patients including 2 cases reported in this study were identified as NEDBA caused by MAPK8IP3 gene variations, including 16 cases with missense mutations and 2 cases with truncation mutations. Among them, 7 patients carried c.1732C>T(p.Arg578Cys) and 5 patients carried c.3436C>T(p.Arg1146Cys). The main clinical manifestations of the 18 patients included developmental delay/intellectual disability (18 cases), poor or absent speech (11 cases), abnormal neurological examination (10 cases: 6 with spastic paraplegia, 2 with spasticity, 2 with ataxia, 1 with unstable gait), hypotonia (10 cases), skeletal malformations (10 cases: 4 with short stature, 3 with scoliosis, 1 with 5th finger clinodactyly and brachydactylky, 1 with flat-valgus feet, 1 with hip subluxation), seizures (3 cases), left hearing loss (1 case), myopic astigmatism and pseudostrabismus (1 case), abnormal brain magnetic resonance imaging (15 cases). Conclusions:Patients with NEDBA is usually characterized by global developmental delay apparent from infancy or early childhood, resulting in language and motor disorders. Additional features may include hypotonia, spasticity, skeletal malformations and abnormal brain magnetic resonance imaging. Currently, missense variations are frequent among the heterozygous MAPK8IP3 genotypes, among which c.1732C>T(p.Arg578Cys) and c.3436C>T(p.Arg1146Cys) are considered hot spot variations.

Objective:To explore the clinical phenotypes and genetic characteristics of a pedigree with Distal arthrogryposis type 5D (DA5D) caused by compound heterozygous variants in the ECEL1 gene. Methods:A child (proband) diagnosed with DA5D and his family members (proband′s parents and sister) who was admitted to the Department of Rehabilitation Medicine of Henan Children′s Hospital in July 2022 due to " multiplex distal arthrogryposis" were enrolled into this study. Clinical data of the proband were collected and peripheral blood samples were obtained from the proband and members of his family about 3 mL. Trio-whole genome sequencing (trio-WGS) was carried out to detected the genetic variations of the proband and his family members. The candidate′s pathogenic gene variants were screened and analyzed by Genome Aggregation Database (gnomAD) and other databases. The screened variants wer annotated for clinical phenotypes using databases like the Online Mendelian Inheritance in Man (OMIM). The pathogenicity of the candidate variants was predicted by bioinformatics tools such as Provean. Based on the guidelines of the American College of Medical Genetics and Genomics (ACMG), pathogenicity ratings were conducted for variant sites. The protein conservation and mutation structure prediction of ECEL1 protein among species were carried out though MEGA-X and PyMOL. The research protocol of this study was reviewed by the Ethics Committee of Henan Provincial Children′s Hospital (Approval No. 2023-H-H01), and informed consent for clinical research was obtained from the guardians of the probands.Results:The proband had multiplex distal arthrogryposis involving hands, feet, knees, and ankles, and had right ptosis, micrognathia, low auricular position, and upturned nose. The parents and sister both had normal phenotypes. Trio-WGS and Sanger sequencing revealed that the child had compound heterozygous variants of paternal c. 1742_c.1743insT and maternal c. 2314T>G, for which the father and sister were carriers of the c. 1742_c.1743insT heterozygous variant and the mother was carrier of c. 2314T>A. Neither mutation site has been reported. According to guidelines of ACMG, the c. 1742_c.1743insT variant was classified as likely pathogenic (PSV1+ PM2_Supporting), and c. 2314T>G was classified as uncertain (PM2_Supporting+ PM3+ PP3). The results of conserved analysis of amino acid residue sequences of ECEL1 protein showed that the missense mutation of the maternal c. 2314T>G(p.Cys772Gly) was highly conserved among humans and other seven species. The protein structure prediction revealed that the c.1742_c.1743insT frameshift mutation led to the protein truncation, and the c. 2314T>G missense mutation resulted in the failure of forming 1 disulfide bond.Conclusion:The compound heterozygous variants of ECEL1 gene were considered to be pathogenic for this DA5D patient, which have expanded the mutational spectrum of the ECEL1 gene and provided a reference for clinical diagnosis as well as genetic counseling for this family.

Objective:To summarize the clinical and genetic characteristics of patients with neurodevelopmental disorder with or without variable brain abnormalities (NEDBA) caused by MAPK8IP3 gene variation. Methods:The clinical data and genetic testing results of 2 children with NEDBA treated in Henan Children′s Hospital from August 2019 to January 2022 were collected retrospectively. Literature was searched and reviewed from China National Knowledge Infrastructure, Wanfang Data Knowledge Service Platform, PubMed database and OMIM database (up to October 2024) with" MAPK8IP3 gene ""NEDBA ""neurodevelopmental disorders "as the search terms. The main clinical genetic characteristics of NEDBA caused by MAPK8IP3 gene variation were summarized. Results:The 2 children, a boy aged 1 year and 8 months and a girl aged 1 year and 4 months, both showed global developmental delay and the onset of the disease in infancy. The de novo heterozygous mutation c.1732C>T(p.Arg578Cys) of the MAPK8IP3 gene was detected by whole-exome sequencing. Case 1 was followed up to 3 years and 10 months old, who had severe developmental delay and was accompanied by hip subluxation and strephexopodia. Literature search retrieved 0 Chinese literature and 2 English literatures. A total of 18 patients including 2 cases reported in this study were identified as NEDBA caused by MAPK8IP3 gene variations, including 16 cases with missense mutations and 2 cases with truncation mutations. Among them, 7 patients carried c.1732C>T(p.Arg578Cys) and 5 patients carried c.3436C>T(p.Arg1146Cys). The main clinical manifestations of the 18 patients included developmental delay/intellectual disability (18 cases), poor or absent speech (11 cases), abnormal neurological examination (10 cases: 6 with spastic paraplegia, 2 with spasticity, 2 with ataxia, 1 with unstable gait), hypotonia (10 cases), skeletal malformations (10 cases: 4 with short stature, 3 with scoliosis, 1 with 5th finger clinodactyly and brachydactylky, 1 with flat-valgus feet, 1 with hip subluxation), seizures (3 cases), left hearing loss (1 case), myopic astigmatism and pseudostrabismus (1 case), abnormal brain magnetic resonance imaging (15 cases). Conclusions:Patients with NEDBA is usually characterized by global developmental delay apparent from infancy or early childhood, resulting in language and motor disorders. Additional features may include hypotonia, spasticity, skeletal malformations and abnormal brain magnetic resonance imaging. Currently, missense variations are frequent among the heterozygous MAPK8IP3 genotypes, among which c.1732C>T(p.Arg578Cys) and c.3436C>T(p.Arg1146Cys) are considered hot spot variations.

Objective:The decision tree Chi-square automatic interactive detection (CHAID) algorithm and binary Logistic regression analysis were used to construct the risk prediction model of premature ovarian failure (POF) in patients with uterine fibroids complicated with hypertension after surgery, and the results of the risk prediction model were compared and analyzed.Methods:Patients with uterine fibroids complicated with hypertension admitted to Taizhou Hospital of Zhejiang Province from Jan. 2019 to Sep. 2022 were retrospectively analyzed as the research objects. CHAID algorithm and Logistic regression analysis were used to establish risk prediction models, respectively. The area under the curve (AUC) of receiver operating characteristic curve (ROC) was used to compare and evaluate the prediction effects of the two models.Results:A total of 860 patients were collected, including 56 patients with premature ovarian function failure after operation, and the incidence of premature ovarian function failure was 6.51%. CHAID method and Logistic regression analysis showed that uterine myoma surgery, hypertension, smoking or passive smoking, family history of premature ovarian failure, sleep status, physical exercise and history of induced curettage were important influencing factors of premature ovarian failure. The accuracy of risk prediction of decision tree model was 88.2%, and the fitting effect of the model was good. The Logistic regression model Hosmer-Leme-show goodness of fit test showed that the model fit was good. The AUC of Logistic regression model was 0.893 (95% CI: 0.862-0.899), and the AUC of decision tree model was 0.882 (95% CI: 0.856-0.899). The predictive value of the two models was moderate, and there was no significant difference between them ( Z=0.254, P>0.05) . Conclusions:The combination of decision tree and Logistic regression model can find the influencing factors of premature ovarian function failure in patients with uterine fibroids complicated with hypertension after operation from different levels, and the relationship between the factors can be more fully understood. The establishment of a risk model for premature ovarian function failure in patients with uterine fibroids complicated with hypertension after surgery can provide a reference for postoperative intervention in patients with uterine fibroids complicated with hypertension, and more effectively help patients actively prevent and slow down the occurrence and development of POF.

OBJECTIVE: To analyze the clinical phenotype and genetic variant of a child with Snijders Blok-Campeau syndrome (SBCS). METHODS: A child who was diagnosed with SBCS in June 2017 at Henan Children's Hospital 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 the extraction of genomic DNA, which was subjected to trio-whole exome sequencing (trio-WES) and genome copy number variation (CNV) analysis. Candidate variant was verified by Sanger sequencing of his pedigree members. RESULTS: The main clinical manifestations of the child have included language delay, intellectual impairment and motor development delay, which were accompanied with facial dysmorphisms (broad forehead, inverted triangular face, sparse eyebrows, widely spaced eyes, narrow palpebral fissures, broad nose bridge, midface hypoplasia, thin upper lip, pointed jaw, low-set ears and posteriorly rotated ears). Trio-WES and Sanger sequencing revealed that the child has harbored a heterozygous splicing variant of the CHD3 gene, namely c.4073-2A>G, for which both of his parents were of wild-type. No pathogenic variant was identified by CNV testing. CONCLUSION The c.4073-2A>G splicing variant of the CHD3 gene probably underlay the SBCS in this patient.
DNA Copy Number Variations ; Heterozygote ; Pedigree ; Phenotype ; RNA Splicing ; Mutation

OBJECTIVE: To explore the genetic basis for a Chinese pedigree with suspected mitochondrial functional defects through combined next-generation sequencing (NGS), copy number variation sequencing (CNV-seq), and mitochondrial DNA (mtDNA) sequencing. METHODS: Clinical data of the proband and his family members were collected. The patient and his parents were subjected to family-trio whole-exome sequencing (WES), CNV-seq and mtDNA variant detection. Candidate variant was verified by Sanger sequencing. RESULTS: Trio-WES revealed that the proband has carried compound heterozygous variants of the NDUFS1 gene, including a paternally derived c.64C>T (p.R22X) nonsense variant and a maternally derived c.845A>G (p.N282S) missense variant. Both variants may cause loss of protein function. No variant that may cause the phenotype was identified by CNV-seq and mtDNA variant analysis. CONCLUSION Children with suspected mitochondrial disorders may have no specific syndromes or laboratory findings. A comprehensive strategy including mtDNA testing may facilitate the diagnosis and early clinical interventions.
Child ; China ; DNA Copy Number Variations ; Electron Transport ; Humans ; Mutation ; NADH Dehydrogenase/genetics* ; Pedigree

To date, the efficacy of radical surgery (RS) versus conservative surgery (CS) for liver hydatid cysts (LHC) remains controversial. This meta-analysis was conducted to compare the two interventions. PubMed, Embase, and Web of Science were searched from their inceptions until June 2016. Meta-analysis was performed using STATA 12.0 software. We identified 19 eligible studies from 10 countries by retrieval. In total, 1853 LHC patients who received RS were compared with 2274 patients treated by CS. The risk of postoperative overall complication, biliary fistula, and recurrence was significantly lower, and operation time was significantly longer in the RS group. However, no statistically significant differences were found in terms of mortality risk and the duration of hospital stay between RS and CS. No significant publication biases were observed in all the above analyses. In conclusion, RS reduces the rates of postoperative complications and recurrence, whereas no trend toward such a reduction in mortality was observed in LHC patients.
Echinococcosis, Hepatic ; mortality ; surgery ; Humans ; Length of Stay ; statistics & numerical data ; Operative Time ; Postoperative Complications ; epidemiology ; Recurrence ; Treatment Outcome

Objective To detect the serum level of transglutaminase 2 (TG2)-specific IgE (slgE) in patients with atopic dermatitis (AD),and to analyze its correlation with the disease condition.Methods A total of 77 patients with AD were enrolled into this study,including 44 patients aged ≥ 12 years and 33 patients aged ＜ 12 years.Of the 77 patients,20 were diagnosed with intrinsic AD,which was characterized by the absence of sIgE and total serum IgE values ＜ 150 kU/L,and 49 with extrinsic AD characterized by positive (++) or even strongly positive slgE for more than 1 kind of exogenous allergens,or total serum lgE values ≥ 150 kU/L.[mmunocapture-biotinylated detector enzyme immunoassay was performed to detect the serum level of TG2-sIgE in 77 patients with AD,40 adult patients with psoriasis vulgaris (PV) and 30 healthy adult controls.Clinical data on the AD patients were recorded,including age,disease duration,SCORAD score,blood eosinophil count,levels of total IgE and TG2-sIgE.Results The serum levels of TG2-sIgE in AD patients aged ≥ 12 years,AD patients aged ＜ 12 years,PV patients and healthy controls were 1.02 ± 0.2,1.04 ± 0.044,0.93 ± 0.25 and 0.71 ± 0.13,respectively.Additionally,the serum level of TG2-sIgE significantly differed among AD patients aged ≥ 12 years,PV patients and healthy controls (x2 =37.407,P ＜ 0.001),and was significantly higher in both AD patients aged ≥ 12 years and PV patients than in the healthy controls (t =7.38,4.83,respectively,both P ＜ 0.001).Moreover,the intrinsic AD group showed significantly higher TG2-sIgE levels compared with the extrinsic AD group (1.16 ± 0.03 vs.1.02 ± 0.20,t =2.27,P =0.02).The TG2-sIgE level was uncorrelated with the patients' age,disease duration,SCORAD score,blood eosinophil count or serum total IgE levels in AD patients (r =0.03,0.14,-0.04,-0.08,0.06,respectively,all P ＞ 0.05).Conclusion The serum level of TG2-sIgE obviously increases in AD patients,so TG2 may be one kind of autoantigen in AD patients,but there is no significant correlation between the TG2-sIgE level and AD severity.