Objective:X-linked non-syndromic hearing loss is an extremely rare type of hearing impairment. This study conducted a phenotypic and genetic analysis of a family with X-linked dominant inheritance to explore the causes of hearing loss. Methods:Clinical data were collected from a patient with non-syndromic hearing loss who visited the Otorhinolaryngology Department of the First Affiliated Hospital of Zhengzhou University in June 2023. Phenotypic and genetic analyses were performed on family members, including audiometric tests, whole-exome sequencing, and PCR-Sanger sequencing verification. Audiological assessments comprised pure-tone audiometry, impedance audiometry, auditory brainstem response, and otoacoustic emission tests. Results:The affected individuals in this pedigree have X-linked dominant non-syndromic deafness caused by mutations in the SMPX gene. The proband, along with their mother and maternal grandmother, exhibit varying degrees of sensorineural hearing loss. Whole-exome sequencing revealed a novel pathogenic variant, NM_014332.3: c. 133-2A>C, in the SMPX gene in the proband. Sanger sequencing confirmed that the proband, proband's mother, and grandmother all carried this pathogenic variant. Conclusion:This study reports a novel pathogenic variant in the SMPX gene, providing additional medical evidence for the diagnosis and treatment of X-linked dominant inherited non-syndromic hearing loss. It enriches the mutation spectrum of the SMPX gene.
Humans ; Pedigree ; Mutation ; Phenotype ; Male ; Hearing Loss, Sensorineural/genetics* ; Exome Sequencing ; Female ; Adult ; Hearing Loss/genetics* ; Evoked Potentials, Auditory, Brain Stem ; Muscle Proteins

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.

Background:Colorectal cancer(CRC)is a major cause of cancer death worldwide,and about 30%to 35%of CRC arises from the serrated pathway.Aims:To analyze the clinicopathological and histomorphological characteristics of colorectal superficially serrated adenoma(SuSA),and to investigate the malignant transformation potential of SuSA and further elucidate the role of RSPO2 and RSPO3 in its carcinogenic mechanism.Methods:A total of 169 serrated colorectal lesions confirmed pathologically and fulfilling the inclusion criteria were collected from Shanxi Bethune Hospital from February 2019 to May 2023.Among them,there were 84 cases of SuSA,23 sessile serrated lesions(SSL),32 traditional serrated adenomas(TSA),and 30 hyperplastic polyps(HP).Thirty-nine cases of tubular adenoma(TA),32 CRC,and 33 normal colorectal mucosal tissues were served as controls.The clinicopathological and histomorphological parameters were collected and recorded.Immunohistochemical staining was used to detect the protein expressions of RSPO2,RSPO3,p53,MLH1 and β-catenin.Results:Patients with SuSA were male predominance,with a mean age of 51.89 years.The average diameter of the lesions was 0.20 cm,predominantly located in the left colon and rectum,and frequently complicated with other polyps/adenomas.The histomorphological features of SuSA were as follows:the glandular necks and crypt bases exhibited straight tubular structure with low-grade dysplasia;the superficial layer demonstrated a serrated architecture,with or without dysplasia,and contained a variable number of goblet cells.Immunohistochemically,there were no statistically significant differences in RSPO2,RSPO3,and p53 expressions between SuSA and TSA(all P>0.05).A strong positive correlation was observed between RSPO2 and RSPO3 in colorectal lesions,excluding HP.Expressions of MLH1 and β-catenin showed no statistically significant differences between SuSA and other colorectal lesions(all P>0.05).Conclusions:SuSAs are more common in males,occur mostly in the left colon and rectum,and are often associated with other polyps/adenomas.They might be precursors of KRAS-mutated TSA and microsatellite stable CRC with high malignant potential.RSPO2 and RSPO3 might play an important role in the carcinogenesis of SuSA.

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.

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.

Background:Colorectal cancer(CRC)is a major cause of cancer death worldwide,and about 30%to 35%of CRC arises from the serrated pathway.Aims:To analyze the clinicopathological and histomorphological characteristics of colorectal superficially serrated adenoma(SuSA),and to investigate the malignant transformation potential of SuSA and further elucidate the role of RSPO2 and RSPO3 in its carcinogenic mechanism.Methods:A total of 169 serrated colorectal lesions confirmed pathologically and fulfilling the inclusion criteria were collected from Shanxi Bethune Hospital from February 2019 to May 2023.Among them,there were 84 cases of SuSA,23 sessile serrated lesions(SSL),32 traditional serrated adenomas(TSA),and 30 hyperplastic polyps(HP).Thirty-nine cases of tubular adenoma(TA),32 CRC,and 33 normal colorectal mucosal tissues were served as controls.The clinicopathological and histomorphological parameters were collected and recorded.Immunohistochemical staining was used to detect the protein expressions of RSPO2,RSPO3,p53,MLH1 and β-catenin.Results:Patients with SuSA were male predominance,with a mean age of 51.89 years.The average diameter of the lesions was 0.20 cm,predominantly located in the left colon and rectum,and frequently complicated with other polyps/adenomas.The histomorphological features of SuSA were as follows:the glandular necks and crypt bases exhibited straight tubular structure with low-grade dysplasia;the superficial layer demonstrated a serrated architecture,with or without dysplasia,and contained a variable number of goblet cells.Immunohistochemically,there were no statistically significant differences in RSPO2,RSPO3,and p53 expressions between SuSA and TSA(all P>0.05).A strong positive correlation was observed between RSPO2 and RSPO3 in colorectal lesions,excluding HP.Expressions of MLH1 and β-catenin showed no statistically significant differences between SuSA and other colorectal lesions(all P>0.05).Conclusions:SuSAs are more common in males,occur mostly in the left colon and rectum,and are often associated with other polyps/adenomas.They might be precursors of KRAS-mutated TSA and microsatellite stable CRC with high malignant potential.RSPO2 and RSPO3 might play an important role in the carcinogenesis of SuSA.

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.

Clopidogrel is the cornerstone of antiplatelet therapy, but there are ethnic and individual differences in the suppression of platelets. Some patients regularly taking drugs still cannot prevent the recurrence of cardio- and cerebrovascular thrombosis, thereby manifest low drug reactivity, i.e., clopidogrel resistance. Genetic polymorphism is the main reason for individual difference. Genetic testing has been used for evaluating the efficacy of antiplatelet therapy, adjusting therapeutic plan, and predicting the risk of cardio- and cerebrovascular thromboembolic events by determining the genetic polymorphisms related with antiplatelet drugs. This article provides a review for the status quo and countermeasure of clopidogrel resistance predicted by gene testing.
Blood Platelets ; Clopidogrel ; Drug Resistance ; Genetic Testing ; Humans ; Platelet Aggregation Inhibitors ; Ticlopidine

Objective To compare the biomechanical stability of different fixation methods for unstable pelvic fractures, so as to provide references for clinical treatment. Methods An unstable pelvic fracture model (Tile C) with the sacroiliac joint dislocation at one side and the pubic rami fracture was constructed via three-dimensional finite element method. In the front of the pelvis, the fracture models were fixed with anterior pelvic Stoppa approach (ASA),subcutaneous anterior pelvic approach (APA), anterior pelvic ilioinguinal approach (AIA) and anterior pelvic external fixation (AEF),and the rear was fixed with sacroiliac joint screw (SIJS）and posterior tension-band plate (PTP). The Von Mises stress and strain distributions of fracture models fixed by different combinations of fixation approaches were analyzed under simulated standing conditions. Results After the models were applied with 500 N vertical load, the maximum stresses at the fracture sites were all reduced, which were smaller than 10 MPa in the front of the pelvis. The maximum stress at the anterior and posterior part of implants in sequence was ASA＜AIA＜AEF＜APA, and the average displacement under the same stress in sequence was ASA＜AIA＜AEF＜APA. Meanwhile, the maximum stresses at the sacroiliac joint and the posterior part of implants in PTP group were significant smaller than those in SIJS group, and the maximum total displacement and vertical displacement in PTP group were also smaller than those in SIJS group. Conclusions Unstable pelvic fractures could be significantly improved when the fracture was fixed by implants in eight combined methods. However, the overall biomechanical properties of the AIA groups were superior to those of the AEF groups and the APA groups. The stability of PTP groups in the treatment of posterior injury was better than that of SIJS groups.