Deletion of a conserved genomic region associated with adolescent idiopathic scoliosis leads to vertebral rotation in mice.

Adolescent idiopathic scoliosis (AIS) is the most common form of scoliosis, in which spinal curvature develops in adolescence, and 90% of patients are female. Scoliosis is a debilitating disease that often requires bracing or surgery in severe cases. AIS affects 2%-5.2% of the population; however, the biological origin of the disease remains poorly understood. In this study, we aimed to determine the function of a highly conserved genomic region previously linked to AIS using a mouse model generated by CRISPR-CAS9 gene editing to knockout this area of the genome to understand better its contribution to AIS, which we named AIS_CRMΔ. We also investigated the upstream factors that regulate the activity of this enhancer in vivo, whether the spatial expression of the LBX1 protein would change with the loss of AIS-CRM function, and whether any phenotype would arise after deletion of this region. We found a significant increase in mRNA expression in the developing neural tube at E10.5, and E12.5, for not only Lbx1 but also other neighboring genes. Adult knockout mice showed vertebral rotation and proprioceptive deficits, also observed in human AIS patients. In conclusion, our study sheds light on the elusive biological origins of AIS, by targeting and investigating a highly conserved genomic region linked to AIS in humans. These findings provide valuable insights into the function of the investigated region and contribute to our understanding of the underlying causes of this debilitating disease.

Dental erosion caused by silent gastroesophageal reflux disease.

BACKGROUND: Gastroesophageal reflux disease, or GERD, is a relatively common condition, in which stomach acid may be refluxed up through the esophagus and into the oral cavity, resulting in enamel erosion. Symptoms such as belching, unexplained sour taste and heartburn usually alert the patient to the condition. In silent GERD, however, these symptoms do not occur, and enamel erosion of the posterior dentition may be the first indication of GERD. CASE DESCRIPTION: A 30-year-old man came to a dental clinic with enamel erosion on the occlusal surfaces of his posterior teeth and the palatal surfaces of his maxillary anterior teeth. He reported no history of gastrointestinal disease or heartburn. CLINICAL IMPLICATIONS: Enamel erosion may be a clinical sign of silent GERD that allows the dentist to make the initial diagnosis. Referral to a physician or gastroenterologist is necessary to define the diagnosis; however, dental expertise may be essential in distinguishing between differential diagnoses such as bulimia, attrition and abrasion. Successful treatment of this medical condition is necessary before dental rehabilitation can be initiated successfully.