Reconstruction Using Free Vascularized Fibular Grafts after Wide Resection of Humerus Chondrosarcoma in a Patient with Cleidocranial Dysplasia

Cleidocranial dysplasia is characterized by hypoplasia of the clavicles, unerupted teeth, narrow pelvis, short stature, and craniofacial malformations. A cause of this skeletal dysplasia is heterozygous mutations of the runt-related transcription factor 2 gene (Runx2), a master regulator for bone and cartilage development. Chondrosarcoma is a primary malignant bone tumor that is usually treated by wide resection surgery. This report shows a case of a 25-year-old female patient with cleidocranial dysplasia who was affected with chondrosarcoma of the left humerus. We performed wide resection of the tumor and reconstruction of the large bone defect of the humerus using free vascularized fibular grafts. The patient preserved the hand function and activity of daily life as the same level as preoperative condition more than five years after the surgery.

Identification and Functional Characterization of a Novel De Novo RUNX2 Frameshift Mutation Associated With Cleidocranial Dysplasia

BackgroundCleidocranial dysplasia (CCD) is a rare genetic disorder affecting bone and cartilage development. Clinical features of CCD comprise short stature, delayed ossification of craniofacial structures with numerous Wormian bones, underdeveloped or aplastic clavicles and multiple dental anomalies. Several studies have revealed that CCD development is strongly linked with different mutations in Runt-related Transcription Factor 2 (RUNX2) gene. In this study, we report a case with typical CCD presentations. MethodsWe performed genetic testing of participants and found a novel RUNX2 frameshift mutation: c.1550delT in a sporadic case. We also compared the functional activity of the mutant and wild-type RUNX2 through immunofluorescence microscopy and osteocalcin promoter luciferase assay. ResultsBoth mutant RUNX2 and wild‑type RUNX2 protein were similarly confined in the nuclei. The novel mutation caused abrogative transactivation activity of RUNX2 on osteocalcin promoter. ConclusionsWe explored a novel RUNX2 deletion/frameshift mutation in a sporadic CCD patient. This finding emphasizes on crucial role of VWRPY domain in RUNX2 transactivation ability.

Whole-genome analyses identify loci and selective signals associated with body size in cattle

Body size plays a key role in production, health, selection, and environmental adaptation of animals, but the genetic basis of body size variation is not clearly understood. Here, we conducted genome-wide association studies (GWAS) of 15 body size traits using autosomal single nucleotide polymorphisms (SNPs) derived from whole-genome sequences of 31 Brahman cattle and 131 Yunling cattle and identified 20 significant loci, which implicated 18 candidate genes. For ischium width, the most significant SNP was assigned to LCORL, a famous gene controlling body size. For chest width, the most significant SNP was located upstream of BMP5, a secreted ligand of transformation growth factor-beta superfamily of proteins involved in bone and cartilage development. Subsequently, we detected selective sweeps in Brahman cattle using integrated Haplotype Score, composite likelihood ratio, and nucleotide diversity. The results showed CNTNAP5 locus associated with hip cross height and LIMCH1 locus associated with forehead size were in selective signals, which were consistent with higher hip cross height and higher forehead size in Brahman cattle compared with Yunling cattle. Our findings provide genetic insights into variation and selection of body size using GWAS and selective signals and will accelerate future efforts aimed at cattle improvement.

RECESSIVE MULTIPLE EPIPHYSEAL DYSPLASIA: A CASE REPORT

Multiple epiphyseal dysplasia (MED) is characterized by abnormal bone and cartilage development particularly affecting epiphysis of long bones. Individuals with MED present during childhood presents with hip pain, knee pain and waddling gait. The autosomal recessive MED is differentiated from the dominant type by the presence of hands, knees and feet malformations with scoliosis. We present here, a case of autosomal recessive MED, an eleven and half years old boy who presented with pain in knees, difficulty walking, abnormal fingers and abnormal toes. The radiographs of hands, knees and pelvis were suggestive of an abnormal epiphyseal development. After diagnosis, patient was counseled and he was advised analgesics and different exercises.

The Long Noncoding RNA MEG3 Is Downregulated and Inversely Associated with VEGF Levels in Osteoarthritis

Osteoarthritis (OA) is becoming a major public health problem in China, especially considering the increase in average life expectancy of the population. Thus, enhanced understanding of the molecular changes associated with OA is urgently needed to develop more effective strategies for the diagnosis and treatment of this debilitating disease. LncRNAs play an important role in the processes of bone and cartilage development. Maternally expressed gene 3 (MEG3) is a maternally expressed lncRNA and may function as a tumor suppressor by inhibiting angiogenesis. OA is closely associated with angiogenesis and the inhibition of angiogenesis presents a novel therapeutic approach to reduce inflammation and pain in OA. In this study, we detected the mRNA expression of MEG3 and VEGF in articular cartilage samples from 20 OA patients and 10 healthy volunteers by real-time RT-PCR. VEGF protein is detected by ELISA in cartilage samples. The results show that human MEG3 is significantly downregulated in OA patients compared to normal cartilage samples. However, higher levels of VEGF mRNA and protein are found in OA compared to the control. Moreover, MEG3 levels are inversely associated with VEGF levels, suggesting that MEG3 may be involved in OA development through the regulation of angiogenesis.