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Tuberous sclerosis complex is an autosomal dominant disorder that affects several organs in the human body including the brain, heart, kidneys, eyes, skin, and lungs. TSC is characterized by hamartomas, which rarely progress to malignancy in affected organs. The estimated prevalence of TSC is 1 in 6,000 to10,000 live births in western populations. The actual incidence of TSC is not known in the Indian population. However, it seems to be as common in India as in western populations. It is estimated that approximately 68% of TSC cases are due to new mutations.
TSC is due to mutations in two known loci: TSC1 on chromosome 9q34 and TSC2 on chromosome 16p13.3. The genes for both the loci have been isolated and named TSC1 and TSC2. The TSC1 gene contains 21 coding and two leader exons and encodes an 8.6 kb mRNA. It spans 45 kb of genomic DNA and codes for hamartin, a 1164 amino acid protein of moleular mass 130 kDa. The TSC2 encodes a 200 kDa protein, tuberin, and spans 43 kb of genomic DNA. The TSC2 gene consists of 41 coding exons.
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The aim of this work was to
1. Isolate and characterize the 5’ends of the gene, including Promoter of TSC1.
(Identification and characterization of a region that has the promoter of the TSC1 gene will help in designing a suitable strategy to screen for mutations in the patients in this region who do not show any mutations in the coding region. Moreover it will help to understand the regulation of TSC1 gene)
2. Ascertain 20-25 TSC cases.
3. Identify the range and types of mutation in TSC cases.
(It will help locate important domains and also to locate mutational hotspots, in both the genes in patients from Indian population which will be ultimately helpful for molecular diagnosis of TSC)
4. Separate chromosome 9 and 16 linked familial cases using haplotype analysis.
(To find how many of the familial cases are linked to TSC1 and TSC2 genes)
5. Carry out genotype-phenotype correlation.
(To find how different is the severity of the disease when mutations are found in TSC1 gene or TSC2 gene)
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