Chondrodysplasia

BACKGROUND: Beckwith-Wiedemann syndrome (BWS) is an overgrowth disorder that exhibits etiologic genomic imprinting characterized by molecular heterogeneity and phenotypic variability. Associations with localized developmental dysplastic chondromatous lesions and cortical neuronal heterotopias have not previously been described. CASE PRESENTATION: A 33-week gestational age female had an omphalocele and intractable hypoglycemia at birth. The placenta demonstrated placental mesenchymal dysplasia...

Chondrodysplasia is closely associated with low birth weight and increased susceptibility to osteoarthritis in adulthood. Prenatal prednisone exposure (PPE) can cause low birth weight; however, its effect on offspring cartilage development remains unexplored. Herein, rats are administered clinical doses of prednisone intragastrically on gestational days (GDs) 0-20 and underwent long-distance running during postnatal weeks (PWs) 24-28. Knee cartilage is assayed for quality and related index changes on GD20, PW12, and PW28...

There is an emerging body of evidence showing that young patients, post haematopoietic stem cell transplantation (HSCT), can develop skeletal changes that mimic an osteochondrodysplasia process. The key discriminator is that these children have had otherwise normal growth and skeletal development before the therapeutic intervention (HSCT), typically for a haematological malignancy. Herein we present that case of a boy who underwent HSCT for Haemophagocytic Lymphohistiocytosis (HLH) aged 2 years. Following Intervention with HSCT this boy's growth has severely decelerated (stature less than 1st centile matched for age) and he has developed a spondyloepiphyseal dysplasia...

Heterozygous mutations in COL10A1 lead to metaphyseal chondrodysplasia type Schmid (MCDS), a skeletal disorder characterized by epiphyseal abnormalities. Prior analysis revealed impaired trimerization and intracellular retention of mutant collagen type X alpha 1 chains as cause for elevated endoplasmic reticulum (ER) stress. However, how ER stress translates into structural defects remained unclear. We generated a medaka ( Oryzias latipes ) MCDS model harboring a 5 base pair deletion in col10a1 , which led to a frameshift and disruption of 11 amino acids in the conserved trimerization domain...

Heterozygous variants in KIF22, encoding a kinesin-like protein, are responsible for spondyloepimetaphyseal dysplasia with joint laxity, leptodactilic type (lepto-SEMDJL), characterized by short stature, flat face, generalized joint laxity with multiple dislocations, and progressive scoliosis and limb deformity. By targeted gene sequencing analysis, we identified a homozygous KIF22 variant (NM_007317.3: c.146G>A, p.Arg49Gln) in 3 patients from 3 unrelated families. The clinical features appeared similar to those of patients carrying heterozygous KIF22 variant (c...

BACKGROUND: The global increase in the aging population has led to a higher incidence of osteoporosis among the elderly. OBJECTIVE: This study aimed to evaluate the protective properties of pinoresinol diglucoside (PDG), an active constituent of Eucommia ulmoides, against dexamethasone-induced osteoporosis and chondrodysplasia. METHODS: A zebrafish model of osteoporosis was established by exposing larval zebrafish to dexamethasone. The impact of PDG on bone mineralization was assessed through alizarin red and calcein staining...

3-hydroxy-3-methylglutaryl-CoA reductase (HMG-CoA reductase, HMGCR) is one of the rate-limiting enzymes in the mevalonate pathway required for cholesterol biosynthesis. It is an integral membrane protein of the endoplasmic reticulum (ER) but has occasionally been described in peroxisomes. By co-immunofluorescence microscopy using different HMGCR antibodies, we present evidence for a dual localization of HMGCR in the ER and peroxisomes in differentiated human monocytic THP-1 cells, primary human monocyte-derived macrophages and human primary skin fibroblasts under conditions of low cholesterol and statin treatment...

Cherry eye is the common name for prolapse of the nictitans gland, a tear-producing gland situated under the third eyelid of dogs. Cherry eye is characterized by a red fleshy protuberance in the corner of the eye, resembling a cherry. This protrusion is a displacement of the normal gland of the third eyelid, thought to be caused by a defect in the connective tissue that secures the gland in place. Options for treatment may include anti-inflammatory medications in mild cases, but surgical replacement of the gland is usually indicated...

BACKGROUND: Mutations in Slc26a2 cause a spectrum of autosomal-recessive chondrodysplasia with a significant and negligible influence on the quality of life. It has been reported that Slc26a2 deficiency triggers the ATF6 branch of the UPR, which may, in turn, activate the negative regulator of the FGFR3 signaling pathway. However, the correlation between the deletion of Slc26a2 and the augmentation of downstream phosphorylation of FGFR3 has not been investigated in vivo . METHODS: First, we constructed Slc26a2 and Fgfr3 double knockout mouse lines and observed gross views of the born mice and histological staining of the tibial growth plates...

BACKGROUND: Cartilage-related diseases, such as hypoplastic chondrodysplasia a rare genetic disorder that affects newborns, causing abnormal cartilage development and restricted skeletal growth. However, the development of effective treatment strategies for chondrodysplasia still faces significant challenges due to limitations in the controlled drug delivery, biocompatibility, and biodegradability of nanomedicines. METHODS: A biodegradable magnesium doped-silicon based-nanoplatforms based on silicon nanoparticles (MON) was constructed...

Rare diseases are estimated to affect 3.5%-5.9% of the population worldwide and are difficult to diagnose. Genome analysis is useful for diagnosis. However, since some variants, especially missense variants, are also difficult to interpret, tools to accurately predict the effect of missense variants are very important and needed. Here we developed a method, "VarMeter", to predict whether a missense variant is damaging based on Gibbs free energy and solvent-accessible surface area calculated from the AlphaFold 3D protein model...

Syndromes of inherited fibroblast growth factor 23 (FGF-23) excess encompass a wide spectrum that includes X-linked hypophosphataemia (XLH), autosomal dominant and recessive forms of rickets as well as various syndromic conditions namely fibrous dysplasia/McCune Albright syndrome, osteoglophonic dysplasia, Jansen's chondrodysplasia and cutaneous skeletal hypophosphataemia syndrome. A careful attention to patient symptomatology, family history and clinical features, supported by appropriate laboratory tests will help in making a diagnosis...

Thiram, an agricultural insecticide, has been demonstrated to induce tibial dyschondroplasia (TD) in avian species. Circular RNA (circRNAs), a novel class of functional biological macromolecules characterized by their distinct circular structure, play crucial roles in various biological processes and diseases. Nevertheless, the precise regulatory mechanism underlying non-coding RNA involvement in thiram-induced broiler tibial chondrodysplasia remains elusive. In this study, we established a broiler model of thiram exposure for 10 days to assess TD and obtain a ceRNA network by RNA sequencing...

BACKGROUND: Genodermatoses are rare heterogeneous genetic skin diseases with multiorgan involvement. They severely impair an individual's well-being and can also lead to early death. METHODS: During the progress of this review, we have implemented a targeted research approach, diligently choosing the most relevant and exemplary articles within the subject matter. Our method entailed a systematic exploration of the scientific literature to ensure a compre-hensive and accurate compilation of the available sources...

BACKGROUND: Chondrodysplasia punctata (CDP) describes skeletal dysplasia secondary to a variety of genetic underpinnings characterized by cartilaginous stippling from abnormal calcium deposition during endochondral bone formation. Approximately 20%-38% of patients with CDP have cervical spine abnormalities, resulting in stenosis and cord compression. However, approaches to management differ among patients. OBSERVATIONS: The authors present an 18-year-old male with a known history of CDP and cervical kyphosis with worsening paresthesias and increased spasticity...

Disorders of chondrocyte differentiation and endochondral osteogenesis are major underlying factors in skeletal developmental disorders, including tibial dysplasia (TD), osteoarthritis (OA), chondrodysplasia (ACH), and multiple epiphyseal dysplasia (MED). Understanding the cellular and molecular pathogenesis of these disorders is crucial for addressing orthopedic diseases resulting from impaired glycosaminoglycan synthesis. Glycosaminoglycan is a broad term that refers to the glycan component of proteoglycan macromolecules...

Schwartz Jampel syndrome (SJS) is a genetic disorder characterized by myotonia and chondrodysplasia. Mutations of the Perlecan gene (HSPG2), which encodes a key component of the extracellular matrix of muscle, bone, and cartilage is cause for the characteristic dysmorphisms of SJS. Clinically remarkable creatinine phosphokinase (CPK) levels are typical and can be associated with myotonia as an underlying cause in SJS patients. We report a unique case of a symptomatic adverse event of statin use in a SJS patient who demonstrated heightened levels of CPK to baseline following a statin induced myopathy...

Collagenopathies are a group of clinically diverse disorders caused by defects in collagen folding and secretion. For example, mutations in the gene encoding collagen type-II ( COL2A1 ), the primary collagen in cartilage, can lead to chondrodysplasias of various severities. One example is the Gly1170Ser substitution in procollagen-II, which causes precocious osteoarthritis and Legg-Calvé-Perthes disease. Here, we develop and characterize a novel induced pluripotent stem cell-based cartilage model of this disease, including both hetero- and homozygous genotypes...

CHST3-related chondrodysplasia with congenital joint dislocations (CDCJD, #MIM 143095), is a rare genetic skeletal disorder caused by biallelic loss of function variants in CHST3. CHST3 is critical for the sulfation of chondroitin sulfate. This study delineates the clinical presentation of nine individuals featuring the key symptoms of CDCJD; congenital joint (knee and elbow) dislocations, short trunk short stature progressive vertebral anomalies, and metacarpal shortening. Additional manifestations include irregular distal femoral epiphysis, supernumerary carpal ossification centers, bifid humerus, club foot, and cardiac abnormalities...

BACKGROUND: Mutations in PTH1R are associated with Jansen-type metaphyseal chondrodysplasia (JMC), Blomstrand osteochondrodysplasia (BOCD), Eiken syndrome, enchondroma, and primary failure of tooth eruption (PFE). Inheritance of the PTH1R gene can be either autosomal dominant or autosomal recessive, indicating the complexity of the gene. Our objective was to identify the phenotypic differences in members of a family with a novel PTH1R mutation. METHODS: The proband was a 13-year, 6-month-old girl presenting with short stature, abnormal tooth eruption, skeletal dysplasia, and midface hypoplasia...