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.