AJMB  Vol.4 No.3 , July 2014
TSC2 Deletions and Duplications: A Descriptive Study in Iranian Patients Affected with Tuberous Sclerosis
Abstract: Tuberous sclerosis complex (TSC) is an autosomal dominant disorder characterized by formation of benign tumors called hamartomas. Although the TSC is diagnosed based on clinical findings but approximately 85% of individuals who meet diagnostic criteria for TSC a mutation can be identified in TSC2 (69%) and TSC1 (31%). A review of mutation type in TSC1 & TSC2 genes reveals that deletion/duplication assay could be a good screening strategy as a first step in TSC molecular diagnosis. All 41 exons and 5’ untranslated region of TSC2 gene in addition to adjacent PKD1 gene were screened for deletion/duplication in 81 patients DNA samples using multiplex ligation dependent probe amplification (MLPA) method. Deletion/duplication was found in 29 (35.8%) patients, including deletions in 26 (32.0%) patients and duplication in 3 (3.8%). Genotype/phenotype analysis, showed five patients with renal function impairment who have large deletions including PKD gene area. Approximately 65% of cases were sporadic, while the remaining have familial positive history. Deletions/duplications of TSC2 gene were seen in 35.8% of patients with TSC. So it could be concluded that MLPA is a useful testing strategy for molecular screening in sporadic forms of TSC patients. MLPA increased the detection of TSC mutations. MLPA is less expensive, quicker and more precise than direct sequencing and southern blot in the characterization of TSC deletions. This technique is recommended as a standard part of TSC clinical molecular diagnosis.
Cite this paper: Ramandi, H. , Ghaderian, S. , Toosi, P. , Tonekaboni, S. , Ebrahimi, A. and Hatamnejadian, N. (2014) TSC2 Deletions and Duplications: A Descriptive Study in Iranian Patients Affected with Tuberous Sclerosis. American Journal of Molecular Biology, 4, 163-167. doi: 10.4236/ajmb.2014.43018.

[1]   Orlova, K.A. and Crino, P.B. (2010) The Tuberous Sclerosis Complex. Annals of the New York Academy of Sciences, 1184, 87-105.

[2]   Sgro, M., Barozzino, T., Toi, A., et al. (1999) Prenatal Detection of Cerebral Lesions in a Fetus with Tuberous Sclerosis. Ultrasound in Obstetrics Gynecology, 14, 356-359.

[3]   Tonekaboni, S.H., Ebrahimi, A., Ahmadabadi, F., keyhanidoust, Z., Zamani, Gh., Rezvani, M., Amirsalari, S., Tavassoli, A. and Rounagh, A. (2012) Clinical and Para Clinical Manifestations of Tuberous Sclerosis: A Cross Sectional Study on 81 Pediatric Patients. Iranian Journal of Child Neurology, 6, 25-31.

[4]   Hung, C.C., Su, Y.N., Chien, S.C., et al. (2006) Molecular and Clinical Analyses of 84 Patients with Tuberous Sclerosis Complex. BMC Medical Genetics, 7, 72.

[5]   Ess, K.C. (2010) Tuberous Sclerosis Complex: A Brave New World? Current Opinion in Neurology, 23, 189-193.

[6]   O’Callaghan, F.J. and Osborne, J.P. (2000) Advances in the Understanding of Tuberous Sclerosis. Archives of Disease in Childhood, 83, 140-142.

[7]   Jones, A.C., Shyamsundar, M.M., Thomas, M.W., et al. (1999) Comprehensive Mutation Analysis of TSC1 and TSC2-and Phenotypic Correlations in 150 Families with Tuberous Sclerosis. The American Journal of Human Genetics, 64, 1305-1315.

[8]   Jentarra, G.M., Rice, S.G., Olfers, S., et al. (2011) Evidence for Population Variation in TSC1 and TSC2 Gene Expression. BMC Medical Genetics, 12, 29.

[9]   Nellist, M., Verhaaf, B., Goedbloed, M.A., et al. (2001) TSC2 Missense Mutations Inhibit Tuberin Phosphorylation and Prevent Formation of the Tuberin-Hamartin Complex. Human Molecular Genetics, 10, 2889-2898.

[10]   Kozlowski, P., Roberts, P., Dabora, S., et al. (2007) Identification of 54 Large Deletions/Duplications in TSC1 and TSC2 Using MLPA, and Genotype-Phenotype Correlations. Human Genetics, 121, 389-400.

[11]   Oyazato, Y., Iijima, K., Emi, M., et al. (2011) Molecular Analysis of TSC2/PKD1 Contiguous Gene Deletion Syndrome. Kobe Journal of Medical Sciences, 57, E1-E10.

[12]   Wimmer, K., Yao, S., Claes, K., et al. (2006) Spectrum of Single- and Multiexon NF1 Copy Number Changes in a Cohort of 1100 Unselected NF1 Patients. Genes Chromosomes Cancer, 45, 265-276.

[13]   Schouten, J.P., McElgunn, C.J., Waaijer, R., et al. (2002) Relative Quantification of 40 Nucleic Acid Sequences by Multiplex Ligation-Dependent Probe Amplification. Nucleic Acids Research, 30, e57.

[14]   Dabora, S.L., Jozwiak, S., Franz, D.N., et al. (2001) Mutational Analysis in a Cohort of 224 Tuberous Sclerosis Patients Indicates Increased Severity of TSC2, Compared with TSC1, Disease in Multiple Organs. The American Journal of Human Genetics, 68, 64-80.