OBJECTIVE: To explore the genetic etiology of 46 Chinese pedigrees affected with Hereditary multiple exostoses (HME) and provide genetic counseling and reproductive intervention. METHODS: Whole-exome sequencing and Sanger sequencing were carried out on 87 patients from the 46 pedigrees to analyze the variants of EXT1 and EXT2 genes. Pathogenicity of the variants was assessed based on the guidelines from the American College of Medical Genetics and Genomics and Association for Molecular Pathology (ACMG/AMP). Prenatal diagnosis and preimplantation genetic testing (PGT) were provided for couples with identified pathogenic mutations. This study was approved by the Medical Ethics Committee of the hospital (Ethics No.: LL-SC-SG-2014-010). RESULTS: In total 17 and 22 pathogenic variants were respectively identified in the EXT1 and EXT2 genes, among which 5 EXT1 and 12 EXT2 variants were unreported previously. Three patients with no family history were found to harbor de novo variants of the EXT1 gene. Twenty nine couples had opted for PGT or underwent prenatal diagnosis following natural conception, and 17 healthy babies were born. CONCLUSION This study has clarified the genetic etiology of 45 HME pedigrees and identified 17 novel variants, which has enriched the mutational spectrum of the EXT1 and EXT2 genes. Reproductive intervention through PGT and prenatal diagnosis have prevented the recurrence of HME in these families.
Humans ; Female ; Male ; Pedigree ; Exostoses, Multiple Hereditary/diagnosis* ; N-Acetylglucosaminyltransferases/genetics* ; Adult ; Exostosin 1 ; Asian People/genetics* ; Genetic Testing ; Exostosin 2 ; Mutation ; China ; Prenatal Diagnosis ; Pregnancy ; Genetic Counseling ; Preimplantation Diagnosis ; Exome Sequencing ; East Asian People

OBJECTIVE: To investigate the clinical effect the treatment of arthroscopy-assisted calcaneal spur resection combined with plantar fascia release and calcaneal decompression in the treatment of the patients with intractable calcaneal pain. METHODS: The clinical data of 50 patients with intractable heel pain from January 2016 to January 2019 were retrospectively analyzed, including 20 males and 30 females;aged from 40 to 68 years old with an average of (50.12±7.35)years old, the medical history ranged from 1 to 4 years. All patients underwent arthroscopy-assisted calcaneal spur resection combined with plantar fascia release and calcaneal decompression, and were followed up, the duration ranged from 24 to 60 months with an average of(42.00±3.28) months. All patients had obvious heel pain before surgery, and X-ray examinations often showed the presence of calcaneal spurs. In addition to the routine foot examination, the changes in the height and angle of the arch of the foot were also measured pre and post-operatively by X-ray, for the evaluation of clinical effect. The VAS system was used to evaluate the degree of foot pain;the AOFAS scoring system was used to comprehensively evaluate the foot pain, voluntary movement, gait and stability. RESULTS: The VAS decreased from (8.75±1.24) before surgery to (5.15±2.35) at 3 months after surgery, (4.07±2.53) at 6 months after surgery, and (3.95±2.44) at the last fllow-up(P<0.05). The AOFAS score increased from (53.46±4.17) before surgery to(92.46±2.53) at 3 months after surgery, (96.33±2.46) at 6 months after surgery, and (97.05±2.37) at the last follow-up(P<0.05). The arch height was (41.54±1.15) mm before operation and (41.49±1.09) mm after the operation, the difference was not statistically significant(P>0.05). The internal arch angle of the foot arch was (121±6)° before operation and (122±7)° after operation. The difference was not statistically significant(P>0.05). CONCLUSION Arthroscopy-assisted calcaneal bone spurs resection combined with plantar fascia release and calcaneal decompression exhibited great clinical effect for treating intractable heel.
Male ; Female ; Humans ; Adult ; Middle Aged ; Aged ; Heel/surgery* ; Heel Spur/surgery* ; Retrospective Studies ; Calcaneus/surgery* ; Foot Diseases ; Pain ; Endoscopes ; Treatment Outcome

The most reliable and convenient measurement method of tibial posterior slope(TPS) and its biomechanical relationship with posterior cruciate ligament (PCL) are still controversial. For X-ray measurement, it is recommended to use full-length lateral X-ray of the lower extremity in quatrous section, which has advantage of highly repeatable and common in the daily diagnosis and treatment process, but it is only applicable to patients with tibial rotation within 15°. When the rotation exceeds 30°, it is difficult to identify the inner contour of platform and is no applicable. If it is only used for daily diagnosis and treatment evaluation, when tibial rotation angle is less than 15°, lateral knee X-ray also has a certain reference significance, but the accuracy could not meet requirements of higher clinical research. For CT measurement method, it could correct tibial rotation, but using the fitting point to measure tibial posterior slope on three-dimensional CT reconstruction is only applicable to knee joint without degeneration, more osteophyte affects the way of using fitting point to determine the plane of tibia with real tibia platform conformity degree, have some limitations. For measurement of MRI, it could not only correct tibial rotation, but also minimize the effect of osteophytes by using tibial anatomical axis as the reference axis, which is a good measurement method. For the biomechanical relationship between tibial posterior slope and tibial posterior slope, increased tibial posterior slope indirectly alleviates tension of PCL through tibial anterior displacement or directly reduces load on posterior cruciate ligament in tibial osteotomies, suggesting a protective mechanism for tibial posterior slope;in total knee arthroplasty with cruciate ligament preserved, the size of tibial posterior slope will affect roll back mechanism of femur. When affected knee with PCL injury, it should be avoid to release then aggravate injury, and the stress could be alleviated by increasing tibial posterior slope appropriately. There has been no unified conclusion on the range of tibial posterior slope that is most beneficial to PCL. The natural tibial posterior slope is between 7 ° and 10°, which is considered to be the most beneficial to protection of PCL, but further studies are needed according to the differences in patients' bone status, surgical methods and so on.
Arthroplasty, Replacement, Knee/methods* ; Femur/surgery* ; Humans ; Knee Joint/surgery* ; Osteophyte/surgery* ; Posterior Cruciate Ligament/surgery* ; Tibia/surgery*

OBJECTIVE: To explore the genetic basis for a pedigree affected with hereditary multiple osteochondroma (HMO). METHODS: Peripheral blood samples were collected from the proband and members of his pedigree with informed consent. Following extraction of genomic DNA, all coding exons and flanking intronic sequences (-10 bp) of the EXT1 and EXT2 genes were subjected to targeted capture and next generation sequencing (NGS). Suspected variant was verified by Sanger sequencing. RESULTS: A heterozygous nonsense variant (c.1911C>A) was found in exon 10 of the EXT1 gene in the proband and his affected father but not in a healthy sister and normal controls. The variant was classified as a pathogenic based on the guidelines of the American College of Medical Genetics and Genomics (PVS1+PM2+PP1). Bioinformatic analysis predicted that the c.1911C>A variant may be disease-causing via nonsense-mediated mRNA decay and anomalous splicing. CONCLUSION The c.1911C>A variant probably underlay the disease in this pedigree. Discovery of this variant enriched the variant spectrum of HMO.
Codon, Nonsense ; Exons/genetics* ; Exostoses, Multiple Hereditary/genetics* ; Heterozygote ; Humans ; Pedigree

OBJECTIVE: To identify pathogenic variations of EXT1 and EXT2 genes in two Chinese pedigrees affected with hereditary multiple exostosis (HME). METHODS: Genomic DNA was extracted from peripheral blood samples using a phenol-chloroform method. PCR and Sanger sequencing was conducted to amplify the exons and the flanking intronic regions of the EXT1 and EXT2 genes. RESULTS: DNA sequencing has revealed a heterozygous missense variation c.812A>G (p.Tyr271Cys) in the exon 1 of EXT1 in pedigree 1, and a heterozygous frameshift variation c.1431dup (p.Ser478Leufs*43) in the exon 6 of EXT1 in the proband from pedigree 2. Both variations have co-segregated with the disease phenotype, which was also consistent with previous report. CONCLUSION Two heterozygous pathogenic variations underlying HME have been identified. The result has facilitated genetic counseling and prenatal diagnosis for the affected pedigrees.
Asian Continental Ancestry Group ; Base Sequence ; DNA Mutational Analysis ; Exostoses, Multiple Hereditary ; genetics ; pathology ; Frameshift Mutation ; Humans ; Mutation, Missense ; N-Acetylglucosaminyltransferases ; genetics ; Pedigree

OBJECTIVE: To detect EXT1 and EXT2 gene mutations in two pedigrees affected with hereditary multiple exostosis (HME). METHODS: The coding regions and exon/intron boundaries of the EXT1 and EXT2 genes were analyzed by targeted next-generation sequencing (NGS). Suspected mutations were confirmed by Sanger sequencing of the probands, their family members and 200 unrelated healthy controls. Gross deletion was confirmed by quantitative PCR (qPCR) analysis and multiple ligation-dependent probe amplification (MLPA) analysis. RESULTS: Two mutations were detected in the pedigrees, which included EXT2 gene c.337_338insG mutation in pedigree 1 and deletion of entire EXT1 in pedigree 2. Analysis of sequencing data revealed that a novel heterozygous mutation (c.337_338insG) in EXT2 gene in proband 1 and his father. The same mutation was not found among healthy family members and 200 unrelated healthy controls. As shown by NGS and MLPA analysis, proband 2 carried a heterozygous deletion of entire EXT1 gene. The same deletion was also found in her mother by qPCR. CONCLUSION Mutations of the EXT1 and EXT2 genes probably underlie the HME in both pedigrees. NGS combined with Sanger sequencing, qPCR and MLPA is effective for attaining the diagnosis.
DNA Mutational Analysis ; Exostoses, Multiple Hereditary ; genetics ; Female ; Humans ; Mutation ; N-Acetylglucosaminyltransferases ; genetics ; Pedigree

Cervical Vertebrae ; Exostoses, Multiple Hereditary ; Humans ; Spinal Cord Compression ; Spinal Osteophytosis

No abstract available.
Exostoses ; Fingers ; Korea

BACKGROUND AND OBJECTIVES: External auditory canal osteoma is an uncommon benign lesion and represents as unilateral solitary pedunculated mass. The aim of this study is to evaluate the clinical symptoms of osteoma and its treatment outcomes over a 10-year period in a tertiary hospital. SUBJECTS AND METHOD: Eight patients underwent operation to remove an external auditory canal osteoma at Chungbuk National University Hospital from 2008 to 2017. The medical records were retrospectively reviewed with regard to clinical characteristics, size and location of osteoma, method of surgery and treatment outcomes. RESULTS: The average age of patients was 41.8 years with the male predominance of 6:2. All of the lesions in the osteoma were unilateral and solitary (average size 5.0 mm). All of the eight cases were pedunculated: in four cases, the stalks of the osteoma were found on the tympanomastoid suture line and in three cases, it was found on the tympanosquamous suture line. Four patients were asymptomatic, where the lesions were found incidentally during unrelated evaluations. No patients were found with conductive hearing loss in the pure tone audiometry. Transcanal and endaural approach were used in five and three cases, respectively. Most of the cases were removed by curettage only, except for the two who needed additional drilling. The average surgery time was 15.6 minutes. There was no postoperative complication or recurrence. CONCLUSION: The external auditory canal osteoma was mostly unilateral and solitary. The removal of osteoma in the early stage was relatively easy with no recurrence or complication.
Audiometry ; Chungcheongbuk-do ; Curettage ; Ear Canal ; Exostoses ; Hearing Loss, Conductive ; Humans ; Male ; Medical Records ; Methods ; Osteoma ; Postoperative Complications ; Recurrence ; Retrospective Studies ; Sutures ; Tertiary Care Centers

Animal models of osteoarthritis (OA) have played a key role in understanding the etiology of OA and in the development of new therapeutic strategies. Although pigs have an advantage as an animal disease model due to their similarity to humans, there are few studies on the induction of OA in minipigs. Therefore, this study aimed to characterize disease progression of OA in total medial meniscectomy (TMM)-operated skeletally mature minipigs, up to day 180 postoperatively. There were no significant alterations in vital signs or hematological indices throughout the observation period. However, clinical manifestations of OA in the medial femoral condyles of TMM-operated minipigs were progressive, depending on postoperative duration, with respect to osteophytes formation and roughened surfaces on radiological observation, cartilage erosion under macroscopic examination, and severe cartilage defects including fibrillation, vertical fissures, and cartilage denuding on histopathological observation, with the highest score indicating late-stage OA on day 180 and without indicating apparent variation between subjects. In particular, the lateral femoral condyles were also degenerated, possibly due to localization of weight-bearing from both menisci to the lateral meniscus. Therefore, TMM in minipigs is suitable for reproducible induction of degenerative changes in the femorotibial joints that closely resemble late-stage OA, and is suitable for use in further research.
Cartilage ; Disease Models, Animal ; Disease Progression ; Humans ; Joints ; Menisci, Tibial ; Models, Animal ; Osteoarthritis ; Osteophyte ; Swine ; Swine, Miniature ; Vital Signs ; Weight-Bearing