Background: and Purpose Vertebrobasilar fusiform aneurysms (VBFAs) carry substantial morbidity and mortality, but optimal management for unruptured VBFAs remains unclear. We compared the safety and efficacy of conservative management (CM), stent-assisted coiling (SAC), and flow diverters (FDs) in patients with unruptured VBFAs, focusing on long-term prognosis. Methods: This study included data from a nationwide Chinese cohort of patients with vertebrobasilar dissecting aneurysms. Inverse probability of treatment weighting (IPTW) balanced confounders across groups. The primary outcome was poor prognosis (modified Rankin Scale score >2). Secondary outcomes included aneurysm rupture, ischemic stroke, compression symptoms, and VBFA-related deaths. Logistic regression estimated odds ratios (ORs) and 95% confidence intervals (CIs). Subgroup and sensitivity analyses were performed. Results: Among 1,115 patients with unruptured VBFAs, 838 (median age, 54 years; 655 men) were included. After IPTW, baseline characteristics were balanced. Median follow-up was 54 months. FD was associated with a lower risk of poor prognosis than CM (OR, 0.48 [95% CI, 0.30 to 0.77]; p=0.002), with no difference between CM and SAC. FD also reduced aneurysm rupture (OR, 0.20 [95% CI, 0.07 to 0.60]; p=0.004) and compression symptoms (OR, 0.30 [95% CI, 0.13 to 0.68]; p=0.004) versus CM. Time-to-event analyses further revealed significant differences in vertebral artery lesions and Type I–II VBFAs, whereas no significant differences were observed in basilar or vertebrobasilar junction lesions or in Type III–IV VBFAs. Conclusions Compared with CM, FD was associated with improved long-term outcomes in unruptured VBFAs, particularly in vertebral artery lesions and Type I–II VBFAs, although residual confounding cannot be excluded.

Objective:The aim of this study is to analyze the clinical characteristics and genetic variants of a late-onset auditory neuropathy pedigree caused by maternally inherited- mitochondrial mutation.Methods:A male proband who presented with bilateral sensorineural hearing loss at Henan Children′s Hospital in September 2023 was chosen, along with his family members (4 generations, 20 individuals) as the study subjects. Data from this pedigree were collected, organized, and analyzed for clinical genetic characteristics. Medical histories were obtained from family members, pedigree charts were drawn, audiological, imaging, and physical examinations were conducted. Pathogenic genes and mutations were screened using high-throughput sequencing. Sanger sequencing was employed for variant confirmation and segregation validation in the family.Results:In this family, a total of 12 members (10 members collected) had sensorineural hearing loss, characterized by late-onset hearing impairment with an onset age ranging from 9 to 30 years. The patients exhibited poor speech recognition rates, and audiometric examinations are consistent with auditory neuropathy. There was no history of ototoxic drug use. High-throughput sequencing identified the variant NC_012920.1:m.7471dup in the mitochondrial MT-TS1 gene as the pathogenic variant. Sanger sequencing results confirmed that the pathogenic gene mutation site perfectly co-segregated with the auditory neuropathy phenotype in this family. According to the classification criteria and guidelines for genetic variations by the American College of Medical Genetics and Genomics, the variant was classified as a pathogenic mutation. Conclusion:The mitochondrial MT-TS1 gene mutation m.7471dup is considered to be the pathogenic cause in this late-onset auditory neuropathy pedigree.

Objectiv To investigate an autosomal dominant non-syndromic hearing loss family pedigree com-prehensively,aiming to precisely define its clinical phenotypes and uncover the underlying molecular genetic etiolo-gy.Methods A detailed interrogation of the proband's medical history and family history was conducted.Physical examinations,audiological assessments and temporal bone CT scans were performed.Genomic DNA was extracted from the peripheral blood of the proband(Ⅳ-8)for whole-exome sequencing(WES).Subsequently,candidate vari-ants identified through WES were validated among family members using Sanger sequencing.Results There were 36 individuals in 4 generations in this family pedigree,showing autosomal dominant inheritance.Among them,16 individuals presented with progressive hearing loss.Audiological examinations were completed for 13 of them,re-vealing normal hearing in three individuals(Ⅲ-1,Ⅲ-1 1,Ⅳ-4)and bilateral symmetric hearing loss of varying se-verity in the remaining ten(Ⅱ-2,Ⅱ-4,Ⅱ-10,Ⅲ-4,Ⅲ-10,Ⅲ-13,Ⅲ-14,Ⅳ-1,Ⅳ-7,Ⅳ-8),and the degree of hearing loss was related to age.WES of Ⅳ-8 revealed that she carried the variant NM_199330.2(HOMER2):c.1064 A＞G(p.Ter354Trpext10),and Sanger sequencing verified the variation at this site.Peripheral blood samples of 18 individuals in this family were collected in total.All affected individuals(Ⅱ-2,Ⅱ-4,Ⅱ-10,Ⅲ-4,Ⅲ-9,Ⅲ-10,Ⅲ-13,Ⅲ-14,Ⅳ-1,Ⅳ-7,Ⅳ-8)carried the HOMER2 c.1064 A＞G variant,except for one young member(Ⅳ-6)who had not yet developed hearing loss.Unaffected individuals(Ⅱ-5,Ⅲ-1,Ⅲ-5,Ⅲ-11,Ⅳ-2,Ⅳ-4)lacked the variant,demonstrating complete cosegregation of genotype and phenotype.According to ACMG guide-lines,this variant was classified as likely pathogenic(PM2+PP1+PM4).Conclusion The c.1064 A＞G(p.Ter354Trpext10)variant of the HOMER2 gene is the molecular genetic etiology of this hereditary deafness family pedigree.

Objectiv To investigate an autosomal dominant non-syndromic hearing loss family pedigree com-prehensively,aiming to precisely define its clinical phenotypes and uncover the underlying molecular genetic etiolo-gy.Methods A detailed interrogation of the proband's medical history and family history was conducted.Physical examinations,audiological assessments and temporal bone CT scans were performed.Genomic DNA was extracted from the peripheral blood of the proband(Ⅳ-8)for whole-exome sequencing(WES).Subsequently,candidate vari-ants identified through WES were validated among family members using Sanger sequencing.Results There were 36 individuals in 4 generations in this family pedigree,showing autosomal dominant inheritance.Among them,16 individuals presented with progressive hearing loss.Audiological examinations were completed for 13 of them,re-vealing normal hearing in three individuals(Ⅲ-1,Ⅲ-1 1,Ⅳ-4)and bilateral symmetric hearing loss of varying se-verity in the remaining ten(Ⅱ-2,Ⅱ-4,Ⅱ-10,Ⅲ-4,Ⅲ-10,Ⅲ-13,Ⅲ-14,Ⅳ-1,Ⅳ-7,Ⅳ-8),and the degree of hearing loss was related to age.WES of Ⅳ-8 revealed that she carried the variant NM_199330.2(HOMER2):c.1064 A＞G(p.Ter354Trpext10),and Sanger sequencing verified the variation at this site.Peripheral blood samples of 18 individuals in this family were collected in total.All affected individuals(Ⅱ-2,Ⅱ-4,Ⅱ-10,Ⅲ-4,Ⅲ-9,Ⅲ-10,Ⅲ-13,Ⅲ-14,Ⅳ-1,Ⅳ-7,Ⅳ-8)carried the HOMER2 c.1064 A＞G variant,except for one young member(Ⅳ-6)who had not yet developed hearing loss.Unaffected individuals(Ⅱ-5,Ⅲ-1,Ⅲ-5,Ⅲ-11,Ⅳ-2,Ⅳ-4)lacked the variant,demonstrating complete cosegregation of genotype and phenotype.According to ACMG guide-lines,this variant was classified as likely pathogenic(PM2+PP1+PM4).Conclusion The c.1064 A＞G(p.Ter354Trpext10)variant of the HOMER2 gene is the molecular genetic etiology of this hereditary deafness family pedigree.

Objective To analyze the clinical phenotypes and genetic variants of three families with NOG-re-lated symphalangism spectrum disorder(NOG-SSD).Methods Clinical data of 11 family members from three NOG-SSD families were retrospectively analyzed,including medical history,physical examination,imaging studies,and audiological evaluations.Genomic DNA was extracted from peripheral blood samples of family members for whole-exome sequencing.Results Among the 11 family members,four exhibited mixed or conductive hearing loss.Probands from family 1 and 2 presented with mixed hearing loss,proximal symphalangism,flexion impairment of the fifth interphalangeal joint,and absence of skin creases.The proband and her mother in family 3 displayed con-ductive/mixed hearing loss,proximal symphalangism,and characteristic facial features(semicylindrical nose,hypo-plastic alae nasi,and thin upper lip with vermilion border).Whole-exome sequencing identified pathogenic variants in the NOG gene(NM_005450.6)in all three families.Family 1 and 2 harbored the novel missense variant c.236T＞A(p.Met79Lys)and nonsense variant c.666C＞G(p.Tyr222Ter),respectively,while family 3 carried the frameshift variant c.31del(p.Leu11SerfsTer51).All three variants were classified as pathogenic or likely pathogen-ic and have not been previously reported.Patients in family 1 and 2 were diagnosed with proximal symphalangism-1(SYM 1),whereas those in family 3 were diagnosed with multiple synostoses syndrome-1(SYNS1).Conclusion The NOG gene variants c.236T＞A,c.666C＞G,and c.31del are causative for NOG-SSD in these three families.

Objective:The aim of this study is to analyze the clinical characteristics and genetic variants of a late-onset auditory neuropathy pedigree caused by maternally inherited- mitochondrial mutation.Methods:A male proband who presented with bilateral sensorineural hearing loss at Henan Children′s Hospital in September 2023 was chosen, along with his family members (4 generations, 20 individuals) as the study subjects. Data from this pedigree were collected, organized, and analyzed for clinical genetic characteristics. Medical histories were obtained from family members, pedigree charts were drawn, audiological, imaging, and physical examinations were conducted. Pathogenic genes and mutations were screened using high-throughput sequencing. Sanger sequencing was employed for variant confirmation and segregation validation in the family.Results:In this family, a total of 12 members (10 members collected) had sensorineural hearing loss, characterized by late-onset hearing impairment with an onset age ranging from 9 to 30 years. The patients exhibited poor speech recognition rates, and audiometric examinations are consistent with auditory neuropathy. There was no history of ototoxic drug use. High-throughput sequencing identified the variant NC_012920.1:m.7471dup in the mitochondrial MT-TS1 gene as the pathogenic variant. Sanger sequencing results confirmed that the pathogenic gene mutation site perfectly co-segregated with the auditory neuropathy phenotype in this family. According to the classification criteria and guidelines for genetic variations by the American College of Medical Genetics and Genomics, the variant was classified as a pathogenic mutation. Conclusion:The mitochondrial MT-TS1 gene mutation m.7471dup is considered to be the pathogenic cause in this late-onset auditory neuropathy pedigree.

Objective To analyze the clinical phenotypes and genetic variants of three families with NOG-re-lated symphalangism spectrum disorder(NOG-SSD).Methods Clinical data of 11 family members from three NOG-SSD families were retrospectively analyzed,including medical history,physical examination,imaging studies,and audiological evaluations.Genomic DNA was extracted from peripheral blood samples of family members for whole-exome sequencing.Results Among the 11 family members,four exhibited mixed or conductive hearing loss.Probands from family 1 and 2 presented with mixed hearing loss,proximal symphalangism,flexion impairment of the fifth interphalangeal joint,and absence of skin creases.The proband and her mother in family 3 displayed con-ductive/mixed hearing loss,proximal symphalangism,and characteristic facial features(semicylindrical nose,hypo-plastic alae nasi,and thin upper lip with vermilion border).Whole-exome sequencing identified pathogenic variants in the NOG gene(NM_005450.6)in all three families.Family 1 and 2 harbored the novel missense variant c.236T＞A(p.Met79Lys)and nonsense variant c.666C＞G(p.Tyr222Ter),respectively,while family 3 carried the frameshift variant c.31del(p.Leu11SerfsTer51).All three variants were classified as pathogenic or likely pathogen-ic and have not been previously reported.Patients in family 1 and 2 were diagnosed with proximal symphalangism-1(SYM 1),whereas those in family 3 were diagnosed with multiple synostoses syndrome-1(SYNS1).Conclusion The NOG gene variants c.236T＞A,c.666C＞G,and c.31del are causative for NOG-SSD in these three families.

OBJECTIVE: To explore the clinical and genetic characteristics of a Chinese pedigree affected with Multiple synostoses syndrome type 1 (SYNS1). METHODS: Clinical data of the proband and her family members were collected. Genomic DNA was extracted from peripheral blood samples. Whole-exome sequencing (WES) and whole-genome sequencing (WGS) were carried out for the proband and her parents. RESULTS: The pedigree has comprised of 14 members from three generations, of whom six had manifested hearing loss, with other symptoms including proximal symphalangism, hemicylindrical nose, amblyopia, strabismus, brachydactyly, incomplete syndactyly, which fulfilled the diagnostic criteria for SYNS1. WES had detected no pathogenic single nucleotide variants and insertion-deletion (InDel) in the coding region of the NOG gene, whilst copy number variation (CNV) analysis indicated that there was a heterozygous deletion involving the NOG gene. WGS revealed a heterozygous deletion (54171786_55143998) in 17q22 of the proband. The CNV was classified as pathogenic based on the guidelines from the American College of Medical Genetics and Genomics (ACMG). CONCLUSION The heterozygous deletion in 17p22 involving the NOG gene probably underlay the pathogenesis of SYNS1 in this pedigree. Above finding has enriched the mutational spectrum of NOG. CNV should be considered when conventional sequencing has failed to detect any pathogenic variants in such patients.
Female ; Humans ; DNA Copy Number Variations ; East Asian People ; Pedigree ; Synostosis ; Phenotype

Objective:In this study, a gait acquisition and analysis system is developed to provide a cheap, easy-to-use solution for quantitative recording and analysis of patients' gaits.Methods:From April 2017 to October 2018, we collected the gait data of 19 patients with knee osteoarthritis and 19 healthy volunteers in the orthopaedic outpatient department. Among 19 patients, there were 9 males and 10 females, aged 50.1±9.4 years old. Among 19 healthy volunteers, there were 8 males and 11 females, aged 50.7±10.3 years old. Then, from the collected gait data, the static gait features such as gait speed, step length, stride, and dynamic gait features were automatically calculated, and the statistical difference analysis was finished to determine the correlation between these quantitative gait features and knee osteoarthritis.Results:Firstly, the gait data collected by the depth camera was compared with the data from the multi infrared camera-based motion analysis system (gold standard). The average angle error of the collected knee joint angle was 0.98 degrees, which proved the correctness of the gait data recorded by the depth camera. The statistical difference analysis of gait characteristics between the patient group and the healthy group showed that the gait characteristics with P<0.05 included: gait speed ( r=-0.922, P<0.001), step length ( r=-0.897, P=0.004), stride ( r=-0.914 , P<0.001), dynamic characteristics of angle of knee joint ( r=0.775, P=0.001). Conclusion:The gait acquisition and analysis system based on the depth camera can accurately record and store the gait data of the patients with knee osteoarthritis. Moreover, the extracted quantitative gait features have statistical differences between the patients and the healthy group, which is helpful for the gait analysis of bone joint.

The Genome Warehouse (GWH) is a public repository housing genome assembly data for a wide range of species and delivering a series of web services for genome data submission, storage, release, and sharing. As one of the core resources in the National Genomics Data Center (NGDC), part of the China National Center for Bioinformation (CNCB;https://ngdc.cncb.ac.cn), GWH accepts both full and partial (chloroplast, mitochondrion, and plasmid) genome sequences with different assembly levels, as well as an update of existing genome assemblies. For each assembly, GWH collects detailed genome-related metadata of biological project, biological sample, and genome assembly, in addition to genome sequence and annotation. To archive high-quality genome sequences and annotations, GWH is equipped with a uniform and standardized procedure for quality control. Besides basic browse and search functionalities, all released genome sequences and annotations can be visualized with JBrowse. By May 21, 2021, GWH has received 19,124 direct submissions covering a diversity of 1108 species and has released 8772 of them. Collectively, GWH serves as an important resource for genome-scale data management and provides free and publicly accessible data to support research activities throughout the world. GWH is publicly accessible at https://ngdc.cncb.ac.cn/gwh.