XPD

XPD

XPD, short for Xeroderma Pigmentosum complementation group D, is a rare genetic disorder that affects the body's ability to repair DNA damage caused by ultraviolet (UV) radiation. It is classified as a type of nucleotide excision repair disorder, which means that individuals with XPD have a defect in the DNA repair mechanism responsible for removing UV-induced DNA lesions.

Symptoms

People with XPD often exhibit a range of symptoms, which can vary in severity depending on the individual. The most common symptoms include:

1. Extreme sensitivity to sunlight: Individuals with XPD are highly susceptible to sunburns and other skin damage caused by even minimal exposure to UV radiation. This sensitivity can lead to the development of freckles, dry skin, and premature aging.

2. Eye problems: XPD can also affect the eyes, causing photophobia (sensitivity to light), dryness, and irritation. In severe cases, it can lead to vision loss or blindness.

3. Neurological abnormalities: Some individuals with XPD may experience neurological symptoms, such as developmental delays, intellectual disability, hearing loss, and difficulties with coordination and balance.

4. Increased risk of skin cancer: Due to the impaired DNA repair mechanism, people with XPD have a significantly higher risk of developing skin cancer, particularly melanoma and non-melanoma skin cancers.

Causes

XPD is caused by mutations in the XPD gene, also known as ERCC2 (Excision Repair Cross-Complementation Group 2). This gene provides instructions for producing a protein called XPD, which is a crucial component of the nucleotide excision repair pathway. Mutations in the XPD gene disrupt the normal functioning of this pathway, leading to the accumulation of DNA damage and the development of XPD symptoms.

XPD is an autosomal recessive disorder, which means that an individual must inherit two copies of the mutated XPD gene (one from each parent) to develop the condition. If only one copy of the gene is mutated, the person is considered a carrier and does not typically exhibit symptoms.

Diagnosis

Diagnosing XPD involves a combination of clinical evaluation, genetic testing, and assessment of the individual's response to UV radiation. Skin biopsies may be performed to examine the DNA repair capacity of the patient's cells. Genetic testing can confirm the presence of XPD mutations.

Treatment

Currently, there is no cure for XPD. Treatment primarily focuses on managing the symptoms and minimizing exposure to UV radiation. This includes:

1. Sun protection: Individuals with XPD should avoid direct sunlight, especially during peak hours. Protective clothing, hats, and sunglasses should be worn to shield the skin and eyes from UV radiation.

2. Sunscreen: Regular application of a broad-spectrum sunscreen with a high sun protection factor (SPF) is essential to protect the skin from UV damage.

3. Regular check-ups: Individuals with XPD should undergo regular skin examinations to detect any signs of skin cancer at an early stage.

4. Genetic counseling: Genetic counseling is recommended for individuals with XPD and their families to understand the inheritance pattern and the risk of passing on the condition to future generations.

Research and Future Directions

Ongoing research aims to better understand the underlying mechanisms of XPD and develop potential treatments. Gene therapy and targeted molecular therapies are being explored as potential avenues for intervention. Additionally, advancements in sunscreen technology and protective clothing may help improve the quality of life for individuals with XPD.

See Also

• Nucleotide excision repair
• Ultraviolet radiation
• Skin cancer