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*

The human homologue of mouse progressive ankylosis protein(ANKH)is an inorganic pyrophosphate transport regulator,which regulates tissue mineralization by controlling the level of inorganic pyrophosphate.It plays an important role in the pathogenesis and development of bone and joint diseases,such as ankylosing spondylitis,craniometaphyseal dysplasia,and articular cartilage calcification.This review summarizes the progress of research on ANKH and the above-mentioned diseases.
Ankylosis ; Humans ; Hyperostosis ; Hypertelorism ; Joint Diseases ; Mice ; Mutation

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

Acquired Hyperostosis Syndrome/surgery* ; Humans ; Tonsillectomy

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

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

STUDY DESIGN: Retrospective study.OBJECTIVES: To compare the degeneration of sacroiliac joint (SIJ) following lumbar or lumbosacral fusion.SUMMARY OF LITERATURE REVIEW: The SIJ is adjacent to lumbosacral junction and its degeneration can be the potential cause of pain. However, the study addressing SIJ degeneration following lumbar or lumbosacral fusion is very limited.MATERIALS AND METHODS: From June 2002 to June 2012, 98 patients who underwent posterior decompression and posterolateral fusion were included in this study. The study group was divided into 2 groups according to the range of fusion. Group A had fusion to L5 and included 34 patients. Group B had fusion to S1 and included 64 patients. We evaluated the five years postoperative radiologic and clinical outcomes retrospectively.RESULTS: There was no statistically significant difference of bilateral preoperative subchondral sclerosis and osteophytes of the SIJ between group A and group B. However, group B revealed statistically significant subchondral sclerosis and osteophyte formation of the SIJ than group A on every radiographs after postoperative 1 year. In group B, the number of fusion segments and age were statistically positively correlated with the degeneration of the SIJ.CONCLUSIONS: Degeneration of the SIJ revealed more rapid and more severe progression in lumbosacral fusion group than in lumbar fusion group. The number of fusion segments and age were positively correlated with the degeneration of the SIJ in lumbosacral fusion group. Therefore, these facts should be taken into account when performing spinal fusion.
Decompression ; Humans ; Osteophyte ; Retrospective Studies ; Sacroiliac Joint ; Sclerosis ; Spinal Fusion

Age estimation from skeletal remains is an important step in forensic biological identification. The main objective of this study is to develop an age estimation equation for the Thai population from vertebral osteophytes. Each vertebra in the cervical, thoracic and lumbar segments was scored for degree of osteophyte formation. Classification was carried out in accordance with the criteria established by Snodgrass and Watanabe, and used a new modified score of the length of vertebral osteophyte for age estimation. The sample included 400 individuals (262 males, 138 females) ranging in age from 22 to 97 years. A sample of Thai vertebral columns was used, the columns being divided into the following groups of vertebrae: cervical (C2–C7), thoracic (T1–T12), and lumbar (L1–L5). Each vertebra was scored for the degree of osteophyte formation and the accumulated data was analyzed statistically. Correlation coefficients and R-squared from mean in lumbar vertebrae for females of criteria established by the method of Snodgrass and Watanabe, the new modified score by length of vertebral osteophytes were 0.801 and 0.642 (P<0.01); 0.755 and 0.57 (P<0.01); 0.786 and 0.618 (P<0.01), respectively. This study presents all 23 subcategories (C2–L5) of the vertebrae to apply in real situations, showing all age estimation equations for males, females and combined sexes of unknown sex. One application of this study is age estimation when dealing with forensic cases in the Thai population.
Asian Continental Ancestry Group ; Classification ; Female ; Forensic Anthropology ; Forensic Sciences ; Humans ; Lumbar Vertebrae ; Male ; Methods ; Osteophyte ; Research Design ; Spine ; Thailand