TY - JOUR
T1 - The molecular genetics of tuberous sclerosis
AU - Sampson, Julian R.
AU - Harris, Peter C.
PY - 1994
Y1 - 1994
N2 - Tuberous sclerosis (TSC) is an autosomal dominant trait characterized by the widespread development of benign tumours classified as hamartoma, and is often associated with seizures and mental retardation. The patchy distribution and focal nature of the growths suggests that they might result from inactivation of a tumour suppressor gene by a two-hit process. Over the last 2 years, studies designed to investigate both germline and somatic TSC mutations have lent support to this hypothesis. Analysis of TSC-associated hamartomas has shown loss of heterozygosity for the regions of chromosomes 9 and 16 known to harbour TSC genes, consistent with the occurrence of somatic 'second-hit' mutations. Parallel investigations using pulse field gel electrophoresis have identified constitutional deletions representing 'first-hit' mutations at 16p13.3, leading to the rapid identification of one of the causative genes, TSC2. Intriguingly, the TSC2 product, tuberin, has an area of sequence homology with the GTPase activating protein rap1 GAP, suggesting a possible mechanism for its role in regulating cellular growth.
AB - Tuberous sclerosis (TSC) is an autosomal dominant trait characterized by the widespread development of benign tumours classified as hamartoma, and is often associated with seizures and mental retardation. The patchy distribution and focal nature of the growths suggests that they might result from inactivation of a tumour suppressor gene by a two-hit process. Over the last 2 years, studies designed to investigate both germline and somatic TSC mutations have lent support to this hypothesis. Analysis of TSC-associated hamartomas has shown loss of heterozygosity for the regions of chromosomes 9 and 16 known to harbour TSC genes, consistent with the occurrence of somatic 'second-hit' mutations. Parallel investigations using pulse field gel electrophoresis have identified constitutional deletions representing 'first-hit' mutations at 16p13.3, leading to the rapid identification of one of the causative genes, TSC2. Intriguingly, the TSC2 product, tuberin, has an area of sequence homology with the GTPase activating protein rap1 GAP, suggesting a possible mechanism for its role in regulating cellular growth.
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U2 - 10.1093/hmg/3.suppl_1.1477
DO - 10.1093/hmg/3.suppl_1.1477
M3 - Short survey
C2 - 7849741
AN - SCOPUS:0028040522
SN - 0964-6906
VL - 3
SP - 1477
EP - 1480
JO - Human molecular genetics
JF - Human molecular genetics
IS - REVIEW
ER -