Frequency of TSC1 and TSC2 mutations in American, British, Polish and Taiwanese populations

Jóźwiak, Jarosław; Sontowska, Iwona; Płoski, Rafał

doi:10.3892/mmr.2013.1583

Cited by 5 publications

(2 citation statements)

References 18 publications

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“…However, the difference was not statistically significant (P = 0.051) due to the small sample size. All mutation types, including base substitution, insertions, and deletions, were described in TSC and the distribution of mutation spectrums within both genes is highly heterogeneous [7][8][9]12,15,16,29]. The results in our study demonstrated that nonsense mutations occurred significantly more frequently in TSC1 gene (p = 0.001).…”

Section: Discussionmentioning

confidence: 50%

Tuberous Sclerosis Complex in Chinese patients: Phenotypic analysis and mutational screening of TSC1/TSC2 genes

Lin

Zeng

Zhao

et al. 2019

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Tuberous sclerosis complex (TSC) is characterized by the development of hamartomas in multiple organ systems. This study attempted to screen mutations and to investigate the mutation distribution and related phenotypes including epilepsy of Chinese TSC patients. Methods: We performed the genotypic analysis of TSC1 and TSC2 genes in 77 unrelated Chinese TSC patients using direct Sanger sequencing and Multiplex ligation-dependent probe amplification (MLPA). Results: Mutations were identified in a total of 63 (81.8%) cases, including 18 TSC1 mutations (8 nonsense mutations, 6 frameshift, 1 in-frame shift, 1 missense and 2 splice-site) and 45 TSC2 mutations (13 missense, 3 nonsense, 6 splicing, 6 in-frame shift,12 frameshift mutations and 5 large deletions). Large deletions were presented exclusively in TSC2 gene, accounting for 7.9% of all mutations in this study. Fourteen novel mutations were identified in this study. Conclusions: Epilepsy occurs in approximately 75.3% (58/77) of patients. Hypomelanotic macules occurred significantly more often in patients with TSC2 mutations and cases with TSC1/TSC2 mutations had a significantly higher frequency of cortical nodule than patients with no mutations identified. Overall, our data expands the spectrum of mutations associated with the TSC loci and will be of value to the genetic counseling in patients with the disease.

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Section: Discussionmentioning

confidence: 50%

Tuberous Sclerosis Complex in Chinese patients: Phenotypic analysis and mutational screening of TSC1/TSC2 genes

Lin

Zeng

Zhao

et al. 2019

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“…In turn, these promising findings have inspired the investigation of mTOR inhibitors, such as rapamycin, in patients with TSC. Everolimus, an mTOR inhibitor, is now FDA approved for reduction of Subependymal Giant Cell Astrocytomas (SEGAs) in children with TSC 38 . Now, with safety profiles established, several international studies are investigating the use of mTOR inhibitors for improving the cognitive delays and behavioral deficits found in children with TSC 39 .…”

Section: Targeted Treatment Example 1: Tuberous Sclerosis Complexmentioning

confidence: 99%

Diagnosis and Management of Autism Spectrum Disorder in the Era of Genomics

Baker¹,

Jeste²

2015

Pediatric Clinics of North America

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Synopsis While the diagnosis of Autism Spectrum Disorder is based on behavioral signs and symptoms, the evaluation of a child with ASD has become increasingly focused on the identification of the genetic etiology of the disorder. Using chromosomal microarray and whole exome sequencing technology, more than 25% of children with ASD have an identifiable, causative genetic variant or syndrome, and this rate continues to increase with improved methods and widespread use of genetic testing. The identification of genetic variants has been accompanied by a concerted effort to define more homogeneous clinical syndromes that are informed by the underlying genetic etiology of a child’s ASD. In the future, such characterization will facilitate targeted treatments based on mechanisms of disease and common clinical features. In this review we begin with a clinical overview of ASD, highlighting the heterogeneity of the disorder. We then discuss the genetics of ASD and present updated guidelines on genetic testing. We then consider the insights gained from the identification of both single gene disorders and rare variants, with regard to clinical phenomenology and potential treatment targets.

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Pattern of TSC1 and TSC2 germline mutations in Russian patients with tuberous sclerosis

et al. 2018

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Tuberous sclerosis (TS) is a rare autosomal-dominant genetic disease. TS is manifested by the development of multiple hamartomas, which affect brain, kidneys, retina, skin and other organs. This study aimed to reveal specific features of molecular epidemiology of TS in Russia. Blood DNA samples from 61 patients with definite (n = 53) or probable (n = 8) clinical diagnosis of TS were tested for mutations in TSC1 and TSC2 genes using Sanger sequencing and MLPA analysis. Five TSC1/2 mutation-negative patients were further analyzed by exome sequencing. TSC1/2 mutations were detected in 53/61 patients (87%): 39 (74%) carried mutations in the TSC2 and 14 (26%) in the TSC1. Large rearrangements (exon deletions/duplications) affected exclusively TSC2, accounting for 15% of lesions of this gene. 6/8 (75%) patients with incomplete clinical manifestation of TS carried TSC1/2 gene lesion. Overall, 96% of detected germline TSC1/2 mutations occurred de novo. Patients with no mutation identified (NMI) differed from TSC1/2 mutation carriers, being lacking cortical tubers and subependymal nodules but having higher frequencies of renal angiomyolipomas, rhabdomyomas, and lymphangioleiomyomatosis. Exome sequencing failed to identify overt disease-causing mutation candidates among NMI patients. Russian patients with TS have increased frequency of TSC2 large gene rearrangements and TSC1/2 mutations occurring de novo as compared to other studies. Patients with suspected TS diagnosis but NMI status may represent a distinct disease entity.

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Frequency of TSC1 and TSC2 mutations in American, British, Polish and Taiwanese populations

Cited by 5 publications

References 18 publications

Tuberous Sclerosis Complex in Chinese patients: Phenotypic analysis and mutational screening of TSC1/TSC2 genes

Tuberous Sclerosis Complex in Chinese patients: Phenotypic analysis and mutational screening of TSC1/TSC2 genes

Diagnosis and Management of Autism Spectrum Disorder in the Era of Genomics

Pattern of TSC1 and TSC2 germline mutations in Russian patients with tuberous sclerosis

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