TITLE:
TSC2 Deletions and Duplications: A Descriptive Study in Iranian Patients Affected with Tuberous Sclerosis
AUTHORS:
Hossein Ramandi, Sayyed Mohammad Hossein Ghaderian, Parviz Toosi, Seyyed Hassan Tonekaboni, Ahmad Ebrahimi, Nasim Hatamnejadian
KEYWORDS:
Tuberose Sclerosis Complex, TSC2, MLPA, Iran
JOURNAL NAME:
American Journal of Molecular Biology,
Vol.4 No.3,
July
31,
2014
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.