Research updates
15 - Ethics and the Gene Map page 4
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4. The tuberous sclerosis genes Link to the Medical Research Council web site
A story of gene sequencing
Tuberous sclerosis is one of a large number of single gene disorders, just like cystic fibrosis, sickle-cell disease and haemophilia. The story of its mapping and sequencing, as part of the Human Genome Project, is a story of human suffering and competition between scientists, but also a story of human help and scientific collaboration.
Figure 4

Figure 4. Typical appearance of someone with tuberous sclerosis who has facial lesions.


Tuberous sclerosis affects about 1 in 6000 newborn infants. An important feature of the condition is the great variability in its phenotypic manifestation. A typical clinical symptom is the presence of skin lesions on the face (Figure 4), though 15% of those with tuberous sclerosis have no such lesions. These facial lesions superficially resemble acne. However, they do not involve the sebaceous glands. Although these lesions can be quite disfiguring, there are far more serious consequences of tuberous sclerosis.
About 65% of people with tuberous sclerosis have seizures which may be severe. Unfortunately the seizures, especially if they occur within the first 18 months of life, lead to learning difficulties in about 40% of those affected. These learning difficulties can be severe. About a quarter of those with tuberous sclerosis have no speech and about the same proportion display autistic features. Hyperactivity and attention deficit disorders are also common, and destructive behaviour and deliberate self-harm are not infrequent.
Linkage studies showed that two separate genes, one on chromosome-9 and one on chromosome-16 were involved. Each of these two genes is responsible for about half the cases of tuberous sclerosis. The gene on chromosome-16, known as TSC2, was sequenced in 1993 but the gene on chromosome-9, TSC1, proved far harder to sequence. Having spent years unsuccessfully attempting independently to map and sequence it, the research groups in the race agreed in 1996 to collaborate. Sharing all the information between them helped speed progress and success finally came in 1997. Sue Povey describes herself as being "so excited, so excited" the night they realised that they had cracked it. The finding was published on 8 August 1997, in the prestigious journal Science.
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Question 3
About 60% of cases of tuberous sclerosis are due to new mutations. In other words, neither parent has the mutation and yet their child does. However, despite all these new mutations, tuberous sclerosis is not becoming more frequent. Suggest why this is.