A positive correlation between osteopetrosis and genetic disorder of CA II, TCIRG1, SNX10, CLCN7 genes and importance of CRISPR (Cas 9) in gene therapy: A review
Year: 2025
Type: article
Abstract: Osteopetrosis can be defined as a group of uncommon skeletal disorders that are genetically and clinically eterogeneous, often stemming from family history. In osteopetrosis, abnormal osteoclast function disrupts bone homeostasis. Thus, patients have unusually high bone density as their primary symptom, which can lead to easy bone fractures. As a result,the disorderly, excessively dense bone that is brittle continues to grow unregulated. Depending on the inheritance pattern, three distinct types of osteopetrosis have been identified: X-linked osteopetrosis, autosomal recessive osteopetrosis (ARO), and autosomal dominant osteopetrosis (ADO). One of the primary causes of osteopetrosis is the carbonic anhydrase II gene. Carbonic acid is produced from carbon dioxide and water by the enzyme, which is then utilized to produce the acidic surroundings necessary for the breakdown of bone minerals and osteoclast activity. Therefore, autosomal recessive osteopetrosis occurs when genetic alterations bring on a CAII deficit, while CLCN7, TCIRG1, and SNX10 are genes most frequently impacted by osteopetrosis. SNX10 and TCIRG1 have been demonstrated to engage with protons pumped by vacuolar-type H(+)-ATPase (V-ATPase) at the osteoclast contact, respectively, while CLCN7 works in concert with TCIRG1 to transport hydrogen ions outside of the cell. Therefore, defects of these genes cause nonfunctional osteoclasts to induce ineffective bone resorption and, thus, osteopetrosis. Finding genetic mutations in osteopetrosis patients can have significant predictions and therapeutic consequences. In this review, we hope to raise the consciousness of osteopetrosis in medicinal society and encourage more research into potential mutations in CA II, TCIRG1, SNX10, and CLCN7 that may be linked to elevated osteoblast activity and decreased osteoclast activity in patients with osteopetrosis and highlight the importance of the CRISPR technology in gene therapy in the future.
Institutions: University of Misan, Ministry of Health
Language: English
Topic: Bone Metabolism and Diseases
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: diamond
OpenAlex ID: W4409437792