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TSC1 and TSC2 deletions differ in size, preference for recombinatorial sequences, and location within the gene

, : TSC1 and TSC2 deletions differ in size, preference for recombinatorial sequences, and location within the gene. Human Genetics 108(2): 156-166, February

Large TSC gene rearrangements are not rare findings in tuberous sclerosis. Interestingly, all deletions, duplications and inversions so far described involve TSC2, none being associated with TSC1. In order to shed light on the structural basis of the preferential DNA rearrangements in TSC2 over TSC1 and to assess, in an unselected patient population, the prevalence of large re-arrangements in both TSC loci, we screened 202 tuberous sclerosis patients consecutively referred at our center. Southern blot analysis on EcoRI+HindIII double-digested DNA identified 19 partial or full-length gene deletions: three involved TSC1 and sixteen TSC2. The breakpoint sequence of seven internal deletions, three in TSC1 and four in TSC2, allowed us to speculate on the mechanism favoring TSC2 unequal recombinations and to identify a deletion hot spot that lies in TSC1 and that may be relevant in the routine genetic testing of tuberous sclerosis. Briefly, three major features appear to distinguish TSC1 from TSC2 deletions: (1) deletion size: all TSC1 deletions are within the transcriptional unit, whereas 12 of the 16 TSC2 deletions have at least one external breakpoint; (2) location within the gene: all TSC1 deletions are confined to the 3'end of the gene (all three 5' breakpoints being located in intron 20) thus resulting in the same frameshift mutation following amino acid K875, whereas the TSC2 internal breakpoints appear to be scattered along the gene; (3) preference for recombinatorial sequences: six out of eight internal TSC2 breakpoints map within Alu repeats, whereas none of the three TSC1 deletions appear to be Alu-mediated. Indeed, in the latter gene, unique structural features (a purine-rich tract flanked by pyrimidine-rich segments) surrounding one of the two identified breakpoint cluster regions might play a role in promoting inappropriate recombinations.


PMID: 11281455

DOI: 10.1007/s004390100460

Other references

Bradley, D.J., 1998: The next century of tropical health. Tropical Medicine & International Health 3(2): 81-82

Abdel Razel, T.; Said, S.I., 1994: Smooth muscle relaxation by guanylin Implications for mediator role of cyclic GMP in vascular and airway smooth muscle relaxation. FASEB Journal 8(4-5): A556

Skomski, D.; Tempas, C.D.; Cook, B.J.; Polezhaev, A.V.; Smith, K.A.; Caulton, K.G.; Tait, S.L., 2015: Two- and Three-Electron Oxidation of Single-Site Vanadium Centers at Surfaces by Ligand Design. Rational, systematic tuning of single-site metal centers on surfaces offers a new approach to increase selectivity in heterogeneous catalysis reactions. Although such metal centers of uniform oxidation states have been achieved, the ability to con...

Mejbaum Katzenellenbogen, W.; Heimrath, Z., 1965: The level of seromucoids in blood and urine in the course of lipoid nephrosis in children. Seromucoid, that is a protein soluble in the sulpho-salicylic acid (BRS) was studied in three periods of lipoid nephrosis in children: in the acute phase, in the diuretic crisis and in remission. The studies were performed in blood serum, and in u...

Calder, S.Christian.; Davidson, G.R.; Ho, R., 2012: Intentions to consume omega-3 fatty acids: a comparison of protection motivation theory and ordered protection motivation theory. There has been limited research to date into methods for increasing people's intentions to use omega-3 polyunsaturated fatty acids (n-3 PUFA), which have been linked with decreased risk of suffering from numerous major diseases. The present s...

Deepak Patnaik; Sahu, N.P.; Aparna Chaudhari, 2005: Effects of feeding raw soybean meal to fry of Indian major carp, Catla catla, on growth, survival, and protein digestibility. Effect of feeding raw soybean meal on growth, nutrient utilization, and amylase and protease activity of Indian major carp (Catla catla) fry was studied in a 70-day feeding trial. Five isocaloric (1568 kJ/100 g diet) and isonitrogenous (45 g crude...

Mitchell D.K., 1980: Rehabilitation and compensation in new zealand a comparative analysis. Archives of Physical Medicine & Rehabilitation 61(10): 494

Gagel'gans A.I.; Asrarov M.I.; Kazakov I.; Shkinev A.V.; Mirkhodzhaev U.Z.; Mubarakova F.Kh; Tashmukhamedov B.A., 1981: Role of protonophore activity of oxal acetic acid in inducing calcium yield from mitochondria. Oxidation of endogenous PN mitochondria induced by oxalacetic acid (OAA) brings about the release of accumulated Ca2+. Analysis of possible mechanisms of this phenomenon shows that OAA has protonophore activity on mitochondria and BPM [bilayer pho...

Chung, T.; Tittgemeyer, M.; Feldstein Ewing, S.W., 2017: Introduction to the Special Issue: Using neuroimaging to probe mechanisms of behavior change. Neuroimage 151: 1-3

Roth R.A., 1981: Bacitracin an inhibitor of the insulin degrading activity of glutathione insulin transhydrogenase. The antibiotic bacitracin, a known inhibitor of insulin degradation by both isolated cells and subcellular organelles, inhibited the ability of purified glutathione-insulin transhydrogenase to split insulin into its constituent A and B chains. Thi...