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The mysterious gene of MDP syndrome: How does POLD1 gene mutation affect the human body?
MDP syndrome (mandibular hypoplasia with deafness and progeria) is an extremely rare metabolic disorder that prevents the storage of fat tissue under the skin. According to statistics, there are only a few (less than 12) confirmed cases worldwide so far. The latest research shows that the disease may originate from a mutation in the POLD1 gene located on chromosome 19, which causes malfunction of an enzyme that is essential for DNA replication.
Symptoms
The main clinical manifestations of MDP syndrome include mandibular hypoplasia (small jaw), deafness, tight skin, fat deficiency (reduced subcutaneous fat), low testosterone levels in males, contraction of the long tendons in the toes leading to claw toes and joint stiffness. These symptoms become more pronounced with age, especially before puberty.
Genetics
All patients diagnosed with MDP syndrome currently display a consistent genetic mutation, which is a single coding deletion in the POLD1 gene, resulting in the loss of serine at position 605. This change impairs the activity of DNA polymerases but has relatively minor effects on proofreading exonucleases. In 2014, a second genetic variant was reported in a patient in Italy, a newly discovered heteroplasmic mutation in exon 13 (R507C). Most cases are spontaneous gene mutations, meaning that the parents of the patient are usually unaffected.
Diagnostic Methods
The diagnosis of MDP syndrome is based primarily on clinical features and can be confirmed by testing for mutations in the POLD1 gene. Biogenetic teams, such as the one at the Royal Devon Hospital and the University of Exeter in the UK, offer this genetic test and have identified its genetic cause for the first time.
Management and care
Appearance Management
Appearance is normal at birth, but features become more pronounced with age. Management focuses primarily on fat deficiency and slow growth of cartilage and ligaments. Common problems include small noses, small jaws and small ears. Due to insufficient cartilage development, the voice may be high-pitched.
For patients with insufficient fat, facial contours may change significantly, and the lack of fat around the eyes may cause dry eyes and the inability to close during sleep.
Management of Fat Deficiency
Since fat cannot be stored beneath the skin, it is especially important to maintain a healthy diet. It is recommended to choose a low-fat diet and avoid supplementing with too much fat. Exercise is also crucial to increasing the effectiveness of insulin.
Symptoms of Low Testosterone
In male patients, the testicles may not descend and there may be symptoms of low testosterone, most of which may lead to infertility due to insufficient testicular development. Appropriate treatment for these patients may include consideration of testosterone replacement therapy.
Growth and hearing impairment
Although the original description of MDP syndrome referred to short stature, many affected individuals are within the normal height range. Hearing impairment is caused by poor nerve function, and patients often have difficulty wearing hearing aids due to their small ears.
Many people with MDP syndrome perform well intellectually and do not experience a significant reduction in their life expectations.
Foot problems and dental management
Affected persons may develop various problems in their feet, such as hard skin and clawed toes due to lack of subcutaneous fat. Dental management requires the early extraction of crowded teeth to avoid orthodontic difficulties in the future.
Research and Future Prospects
The diagnosis of MDP syndrome was mainly completed by researchers at the University of Exeter Medical School in the UK. The social and cultural influences on patients cannot be ignored. For example, British paracyclist Tom Staniford was reported to suffer from this disease.
Although the characteristics and challenges of MDP syndrome can make life difficult for those with the disorder, scientists and medical professionals continue to conduct research to improve our understanding and treatment of the disorder. We can't help but wonder how genetic mutations play a role in other rare diseases and how future research will change the way we treat medicine?
