Dataset Information

Germline mutation of TSC1 or TSC2 gene in Chinese patients with bilateral renal angiomyolipomas and mutation spectrum of Chinese TSC patients.

ABSTRACT: The germline mutation of the TSC1/2 gene in bilateral renal angiomyolipomas is unclear. Meanwhile, the mutation spectrum of Chinese TSC patients has not been revealed. We recruited 78 patients diagnosed with bilateral renal AMLs. High-throughput sequencing was used to detect any variants in TSC1/2 genes. The results showed that 28.6% of patients diagnosed before 45 were with positive results of TSC1/2 test. The rate decreased to 14.3% for those with onset age over 45. For the 315 previously reported Chinese patients, TSC1 patients were more likely to be affected by nonsense mutations (51.1% vs. 20.7%, p<0.001) and had a significantly higher rate of family history than TSC2 patients (37.8% vs. 19.6%, p=0.0067). Moreover, exon8, 15, and 18 were the hotspot mutation regions for TSC1, and exon 29, 33 and 40 were the most common mutation regions for TSC2. Besides, Chinese TSC patients carried more TSC2 alterations (85.7% vs.76.2%, p<0.001), and were more likely to have a family history than those from TOSCA (22.2% vs. 13.9%, p<0.001). In conclusion, patients affected by bilateral renal AMLs should receive genetic testing of TSC ½ genes and Chinese TSC patients have relatively hotspot mutation regions, which are helpful to genetic counseling and clinical decision making.

SUBMITTER: Jiangyi W

PROVIDER: S-EPMC6977674 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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Germline mutation of TSC1 or TSC2 gene in Chinese patients with bilateral renal angiomyolipomas and mutation spectrum of Chinese TSC patients.

Jiangyi Wang W Gang Guo G Guohai Shi S Dingwei Ye Y

Aging 20200112 1

The germline mutation of the TSC1/2 gene in bilateral renal angiomyolipomas is unclear. Meanwhile, the mutation spectrum of Chinese TSC patients has not been revealed. We recruited 78 patients diagnosed with bilateral renal AMLs. High-throughput sequencing was used to detect any variants in TSC1/2 genes. The results showed that 28.6% of patients diagnosed before 45 were with positive results of TSC1/2 test. The rate decreased to 14.3% for those with onset age over 45. For the 315 previously repo ...[more]

PMID: 31927531

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Project description:Autism spectrum disorder (ASD) is reported in 30 to 60% of patients with tuberous sclerosis complex (TSC) but shared genetic mechanisms that exist between TSC-associated ASD and idiopathic ASD have yet to be determined. Through the small G-protein Rheb, the TSC proteins, hamartin and tuberin, negatively regulate mammalian target of rapamycin complex 1 (mTORC1) signaling. It is well established that mTORC1 plays a pivotal role in neuronal translation and connectivity, so dysregulation of mTORC1 signaling could be a common feature in many ASDs. Pam, an E3 ubiquitin ligase, binds to TSC proteins and regulates mTORC1 signaling in the CNS, and the FBXO45-Pam ubiquitin ligase complex plays an essential role in neurodevelopment by regulating synapse formation and growth. Since mounting evidence has established autism as a disorder of the synapses, we tested whether rare genetic variants in TSC1, TSC2, MYCBP2, RHEB and FBXO45, genes that regulate mTORC1 signaling and/or play a role in synapse development and function, contribute to the pathogenesis of idiopathic ASD.Exons and splice junctions of TSC1, TSC2, MYCBP2, RHEB and FBXO45 were resequenced for 300 ASD trios from the Simons Simplex Collection (SSC) using a pooled PCR amplification and next-generation sequencing strategy, targeted to the discovery of deleterious coding variation. These detected, potentially functional, variants were confirmed by Sanger sequencing of the individual samples comprising the pools in which they were identified.We identified a total of 23 missense variants in MYCBP2, TSC1 and TSC2. These variants exhibited a near equal distribution between the proband and parental pools, with no statistical excess in ASD cases (P > 0.05). All proband variants were inherited. No putative deleterious variants were confirmed in RHEB and FBXO45. Three intronic variants, identified as potential splice defects in MYCBP2 did not show aberrant splicing upon RNA assay. Overall, we did not find an over-representation of ASD causal variants in the genes studied to support them as contributors to autism susceptibility.We did not observe an enrichment of rare functional variants in TSC1 and TSC2 genes in our sample set of 300 trios.

Dataset Information

Germline mutation of TSC1 or TSC2 gene in Chinese patients with bilateral renal angiomyolipomas and mutation spectrum of Chinese TSC patients.

Publications

Germline mutation of TSC1 or TSC2 gene in Chinese patients with bilateral renal angiomyolipomas and mutation spectrum of Chinese TSC patients.

Similar Datasets

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