Mutation and polymorphism analysis of TSC1 and TSC2 genes in Indian patients with tuberous sclerosis complex

Ali, Abdullah Mahmood; Girimaji, Satish Chandra; Markandaya, Manjunath; Shukla, Anil Kumar; Sacchidanand, S; Kumar, Arun

doi:10.1111/j.1600-0404.2004.00366.x

Cited by 25 publications

(17 citation statements)

References 27 publications

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“…The phenotypic manifestations in affected persons vary greatly. In patients meeting standardized (Roach & Sparagana, 2004) clinical criteria for TSC, a disease causing mutation in either TSC1 or TSC2 is found in 75–85% of cases (Dabora et al, 2001; Ali et al, 2005; Sancak et al, 2005; Au et al, 2007).…”

Section: Introductionmentioning

confidence: 99%

“…Even though for most TSC1 and TSC2 mutations there have been no consistent genotype/phenotype correlations between specific mutation types and associated clinical manifestations (Janssen et al, 1990; Niida et al, 1999; Dabora et al, 2001; Humphrey et al, 2004; Ali et al, 2005; Au et al, 2007), many studies show that TSC2 patients have overall both a higher incidence and more severe features of TSC than patients with TSC1 mutations, including more significant neurological, renal and other organ involvement (Jones et al, 1999; Dabora et al, 2001; Langkau et al, 2002; Sancak et al, 2005; Au et al, 2007). However there are also several missense mutations in TSC2 which have been associated with distinctly mild clinical features, such that some family members bearing these TSC2 missense mutations do not fulfill standard diagnostic criteria (Khare et al, 2001; O’Connor et al, 2003; Mayer et al, 2004; Jansen et al,2006).…”

Section: Introductionmentioning

confidence: 99%

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Distinct clinical characteristics of Tuberous Sclerosis Complex patients with no mutation identified

Camposano

Greenberg

Kwiatkowski

et al. 2009

Annals of Human Genetics

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SummaryTuberous Sclerosis Complex (TSC) is a multi-system disorder that is highly variable in its clinical presentation. Current molecular diagnostic methods permit identification of mutations in either TSC1 or TSC2 in 75-85% of TSC patients. Here we examine the clinical characteristics of those TSC patients who have no mutation identified (NMI). A retrospective review of our patient population that had comprehensive testing for mutations in TSC1/TSC2 identified 23/157 (15%) that were NMI. NMI patients had a lower incidence of brain findings on imaging studies, neurological features, and renal findings than those with TSC2 mutations. In contrast, NMI patients had a lower incidence of seizures than TSC patients with TSC1 mutations, but had a higher incidence of both renal angiomyolipomas and pulmonary lymphangioleiomyomatosis. This distinct constellation of findings suggest that NMI patients may have a unique molecular pathogenesis, different from that seen in TSC patients with the usual mutations in TSC1 and TSC2. We suggest that the mechanisms of disease in these patients include both mosaicism for a TSC2 mutation, and unusual non-coding region mutations in TSC2.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Distinct clinical characteristics of Tuberous Sclerosis Complex patients with no mutation identified

Camposano

Greenberg

Kwiatkowski

et al. 2009

Annals of Human Genetics

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“…More than 200 unique TSC1 mutations and 700 unique TSC2 mutations have been reported. In this study, we screened 4 TSC cases for mutations in all coding regions and exon-intron boundaries of the TSC1 and TSC2 genes, and 3 causative mutations in the TSC2 gene were detected in these cases, with a mutation rate of 75%, similar to that obtained previously (Ali et al, 2005;Camposano et al, 2009). van Slegtenhorst et al (1997 reported that approximately 10 to 30% of all TSC cases are due to mutations in the TSC1 gene, but no mutation was found in the TSC1 gene in our study.…”

Section: Discussionmentioning

confidence: 53%

Mutational analyses of the TSC1 and TSC2 genes in cases of tuberous sclerosis complex in Chinese Han children

Gx¹,

Dw²,

Cy³

et al. 2013

Genet. Mol. Res.

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ABSTRACT. Tuberous sclerosis complex (TSC) is an autosomal dominant neurogenetic disorder characterized by hamartomas in multiple organs and is caused by a wide spectrum of mutations in 1 of 2 causative genes (TSC1 or TSC2). Here, we present mutational analyses of the TSC1 and TSC2 genes in 4 cases of TSC in Chinese Han children, including 2 familial and 2 sporadic cases, using PCR and DNA sequencing of the entire coding region as well as exon-intron boundaries of these genes. Three mutations were identified in the TSC2 gene. Of these mutations, 2 mutations (c.3312-3313delGA and c.45delT) were novel, and the 3rd mutation (c.5238-5255del) was previously reported in Chinese Han and other populations. These mutations were not present in healthy family members or in 100 unrelated normal controls. The identification of these mutations in this study further expands the spectrum of known TSC2 gene mutations and contributes to prenatal molecular diagnosis and preimplantation genetic testing of TSC.

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“…In a few studies, where TSC1 and TSC2 promoter region analysis has been performed, the levels of mutations detected were either very low or null 17,18 .…”

Section: Resultsmentioning

confidence: 99%

Mutational analysis of TSC1 and TSC2 genes in Tuberous Sclerosis Complex patients from Greece

Avgeris

Fostira

Vagena

et al. 2017

Sci Rep

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Tuberous sclerosis complex (TSC) is a rare autosomal dominant disorder causing benign tumors in the brain and other vital organs. The genes implicated in disease development are TSC1 and TSC2. Here, we have performed mutational analysis followed by a genotype-phenotype correlation study based on the clinical characteristics of the affected individuals. Twenty unrelated probands or families from Greece have been analyzed, of whom 13 had definite TSC, whereas another 7 had a possible TSC diagnosis. Using direct sequencing, we have identified pathogenic mutations in 13 patients/families (6 in TSC1 and 7 in TSC2), 5 of which were novel. The mutation identification rate for patients with definite TSC was 85%, but only 29% for the ones with a possible TSC diagnosis. Multiplex ligation-dependent probe amplification (MLPA) did not reveal any genomic rearrangements in TSC1 and TSC2 in the samples with no mutations identified. In general, TSC2 disease was more severe than TSC1, with more subependymal giant cell astrocytomas and angiomyolipomas, higher incidence of pharmacoresistant epileptic seizures, and more severe neuropsychiatric disorders. To our knowledge, this is the first comprehensive TSC1 and TSC2 mutational analysis carried out in TSC patients in Greece.

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Mutation and polymorphism analysis of TSC1 and TSC2 genes in Indian patients with tuberous sclerosis complex

Cited by 25 publications

References 27 publications

Distinct clinical characteristics of Tuberous Sclerosis Complex patients with no mutation identified

Distinct clinical characteristics of Tuberous Sclerosis Complex patients with no mutation identified

Mutational analyses of the TSC1 and TSC2 genes in cases of tuberous sclerosis complex in Chinese Han children

Mutational analysis of TSC1 and TSC2 genes in Tuberous Sclerosis Complex patients from Greece

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