Correlative Raman spectroscopy and electron microscopy identifies glycogen rich deposits correlated with local structural defects in long bones of type IV osteogenesis imperfecta patients.

Osteogenesis imperfecta (OI) is a genetic bone disease occurring in approximately 1 in 10,000 births, usually as a result of genetic mutation. OI patients suffer from increased fracture risk and - depending on the severity of the disease - deformation of the limbs, which can even lead to perinatal death. Despite extensive studies, the way in which the genetic mutation is translated into structural and compositional anomalies of the tissue is still an open question.

Acromesomelic Dysplasia With Homozygosity for a Likely Pathogenic BMPR1B Variant: Postaxial Polydactyly as a Novel Clinical Finding.

Background: Acromesomelic chondrodysplasias are a rare subgroup of the clinically and genetically heterogeneous osteochondrodysplasias that are characterised by abnormalities in the limb development and short stature. Here, we report a 2-year-old boy, offspring of consanguineous parents, with acromesomelic dysplasia and postaxial polydactyly in which exome sequencing identified a novel homozygous missense variant in BMPR1B. The patient showed skeletal malformation of both hands and feet that included complex brachydactyly with the thumbs most severely affected, postaxial polydactyly of both hands, shortened toes as well as a bilateral hypoplasia of the fibula.

Radiological and clinical femoroacetabular impingement after slipped capital femoral epiphysis treated by in situ fixation.

Background: The treatment of slipped capital femoral epiphysis (SCFE) is always surgical. In situ fixation (ISF) is widely accepted to stop the epiphysis slipping. Femoroacetabular impingement (FAI) is recognized as a complication after ISF and is one of the major causes of early hip osteoarthritis.

Bizarre Parosteal Osteochondromatous Proliferation With Malignant Transformation and Metastases.

A patient with a benign bizarre parosteal osteochondromatous proliferation (BPOP) located in the anterior knee was treated with resection in preparation for total knee arthroplasty (TKA). The BPOP reoccurred and was treated with re-resection at the time of TKA. The BPOP reoccurred a second time and underwent malignant transformation to a fungating high-grade pleomorphic sarcoma with metastatic lesions.

Radiotherapy Combined With Zoledronic Acid for Fibrous Dysplasia With a Central Giant Cell Granuloma: A Case Report.

Background: Giant cell reparative granulomas are nonneoplastic, benign lesions that can expand and dissolve bone. Fibrous dysplasia is a benign condition in which normal bone tissue is replaced by abnormally proliferating immature reticular bone and fibrous tissue. The combination of giant cell reparative granuloma and fibrous dysplasia is extremely rare and can pose diagnostic and therapeutic challenges because of the complexity of clinical presentation.

Transcriptome-wide RNA m6A methylation profiles in an endemic osteoarthropathy, Kashin-Beck disease.

Kashin-Beck disease (KBD) is a chronic degenerative, disabling disease of the bones and joints and its exact aetiology and pathogenesis remain uncertain. This study is to investigate the role of m6A modification in the pathogenesis of KBD. Combined analysis of m6A MeRIP-Seq and RNA-Seq were used to analyse human peripheral blood samples from three KBD patients and three normal controls (NC).

A novel frameshift deletion variant of ARSL associated with X-linked recessive chondrodysplasia punctata 1: a case report and literature review of prenatal, confirmed cases.

Background: X-linked recessive chondrodysplasia punctata 1 (CDPX1) is a rare congenital skeletal dysplasia characterized by stippled epiphyses, nasal hypoplasia, and brachytelephalangy. ARSL (formerly known as ARSE), a member of the sulfatase gene family located on Xp22.3, has been identified as the causative gene for CDPX1.

Achondroplasia: aligning mouse model with human clinical studies shows crucial importance of immediate postnatal start of the therapy.

Achondroplasia is the most common form of human dwarfism caused by mutations in the FGFR3 receptor tyrosine kinase. Current therapy begins at 2 years of age and improves longitudinal growth but does not address the cranial malformations including midface hypoplasia and foramen magnum stenosis, which lead to significant otolaryngeal and neurologic compromise. A recent clinical trial found partial restoration of cranial defects with therapy starting at 3 months of age, but results are still inconclusive.

A monoallelic variant in CCN2 causes an autosomal dominant spondyloepimetaphyseal dysplasia with low bone mass.

Cellular communication network factor 2 (CCN2) is a secreted extracellular matrix-associated protein, and its aberrantly increased expression has been implicated in a diversity of diseases involving pathological processes of fibrosis, chronic inflammation, or tissue injury, which has promoted the evaluation of CCN2 as therapeutic targets for multiple disorders. However, human phenotypes associated with CCN2 deficiency have remained enigmatic; variants in CCN2 have not yet been associated with a human phenotype. Here, we collected families diagnosed with spondyloepimetaphyseal dysplasia (SEMD), and screened candidate pathogenic genes for families without known genetic causes using next-generation sequencing.

Mutations in fibronectin dysregulate chondrogenesis in skeletal dysplasia.

Fibronectin (FN) is an extracellular matrix glycoprotein essential for the development and function of major vertebrate organ systems. Mutations in FN result in an autosomal dominant skeletal dysplasia termed corner fracture-type spondylometaphyseal dysplasia (SMDCF). The precise pathomechanisms through which mutant FN induces impaired skeletal development remain elusive.

A Single Multiplex PCR and Single-Nucleotide Extension Assay for the Detection of Common Thanatophoric Dysplasia I and II Mutations.

Mutation analysis provides confirmation of a clinical and radiological diagnosis of thanatophoric dysplasia types I and II (TD I and II). We developed a single multiplexed PCR and a single-nucleotide extension (SNE) assay to identify 14 common mutations causing 99% of TD I and TD II, including the challenging three adjacent mutations in the stop codon of exon 18 of the FGFR3 gene. The assay design also provides a solution for resolving SNE PCR product sizing using performance optimized polymer-7.

Complicated Spinal Stenosis and Spinal Deformity in Patients with Achondroplasia: Case Series and Review of the Literature.

Objective: Due to the low incidence of achondroplasia (Ach), there is a relative lack of research on the treatment and management of spinal complications of Ach. Characteristics and interventions for spinal complications in patients with Ach are in urgent need of investigation. This study aimed to summarize the common spinal complications in patients with Ach and the corresponding treatment strategies.