Jensen syndrome is caused by mutations in the TIMM8A gene. This gene provides instructions for making a protein called deafness-dystonia peptide 1 (DDP1), also known as mitochondrial intermembrane space protein 8A.
Here's a breakdown:
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The TIMM8A Gene: This gene is located on the X chromosome. Because males have only one X chromosome, a single mutated copy of TIMM8A is sufficient to cause Jensen syndrome in males. Females, who have two X chromosomes, typically need two mutated copies to be affected, although some females with one mutated copy may show milder symptoms.
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Deafness-Dystonia Peptide 1 (DDP1): This protein plays a crucial role in the transport of other proteins into the mitochondria. Mitochondria are the powerhouses of cells, responsible for generating energy. DDP1 helps other proteins cross the mitochondrial membrane.
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How Mutations Cause Jensen Syndrome: Mutations in TIMM8A disrupt the normal function of DDP1. This impairment in protein transport within the mitochondria leads to mitochondrial dysfunction. This dysfunction particularly affects the nervous system and sensory organs, resulting in the characteristic features of Jensen syndrome, including:
- Deafness (progressive)
- Visual deterioration (progressive)
- Dystonia (involuntary muscle contractions)
- Dementia
- Psychiatric abnormalities
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Relationship to Mohr-Tranebjaerg Syndrome (Deafness-Dystonia Syndrome): Mohr-Tranebjaerg syndrome is also caused by mutations in the TIMM8A gene. However, the specific mutations and their effects on DDP1 may differ, leading to variations in the severity and presentation of the two syndromes. Some consider Jensen syndrome a milder form of Mohr-Tranebjaerg syndrome.
In summary, Jensen syndrome results from mutations in the TIMM8A gene, which disrupts mitochondrial protein transport and leads to the neurological and sensory problems characteristic of the condition.
