EXT2

EXT2 (Exostosin Glycosyltransferase 2) is a gene that in humans is encoded by the EXT2 gene. It is one of the two genes (the other being EXT1) that, when mutated, can lead to the development of Hereditary Multiple Exostoses (HME), a genetic disorder characterized by the formation of multiple osteochondromas, which are benign bone growths that may lead to skeletal abnormalities and have the potential to become malignant.

Function

The EXT2 gene, along with EXT1, is involved in the biosynthesis of heparan sulfate, a critical component of the extracellular matrix that influences a variety of cellular processes including cell division, migration, and differentiation. Heparan sulfate proteoglycans are essential for the normal development and function of tissues and organs. The EXT1 and EXT2 proteins form a complex in the Golgi apparatus, where they catalyze the elongation of the heparan sulfate chains. This activity is crucial for the proper functioning of many signaling pathways that govern embryonic development and the maintenance of tissue homeostasis in adults.

Clinical Significance

Mutations in the EXT2 gene are primarily associated with Hereditary Multiple Exostoses, a condition that is inherited in an autosomal dominant manner. Individuals with HME exhibit multiple osteochondromas, which are cartilage-capped bone tumors that typically arise near the growth plates of long bones. These growths can cause pain, deformities, and, in some cases, compress nerves or other structures, leading to additional complications. The risk of an osteochondroma progressing to a malignant chondrosarcoma is low but significant, necessitating regular monitoring of individuals with HME.

In addition to HME, mutations in EXT2 have been implicated in isolated cases of chondrosarcoma in the absence of multiple exostoses, suggesting a broader role in skeletal tumorigenesis.

Genetic

The EXT2 gene is located on the long (q) arm of chromosome 11 at position 24.1, specifically from base pair 118,611,234 to base pair 118,835,874. Like EXT1, EXT2 mutations can vary widely, including missense mutations, nonsense mutations, and deletions, all of which can disrupt the normal function of the EXT2 protein and lead to the development of HME.

Diagnosis and Management

Diagnosis of HME typically involves a combination of clinical evaluation, family history, and radiographic imaging to identify the presence of multiple osteochondromas. Genetic testing can confirm mutations in the EXT2 gene, providing a definitive diagnosis and allowing for genetic counseling regarding the inheritance pattern and risks to offspring.

Management of HME focuses on monitoring for complications, managing pain, and surgical intervention to remove osteochondromas that cause significant symptoms or functional impairment. Regular follow-up is essential to detect any changes in the osteochondromas that may suggest malignant transformation.

See Also

• Hereditary Multiple Exostoses
• Osteochondroma
• Chondrosarcoma
• Extracellular matrix
• Heparan sulfate