Genotype-phenotype correlation of patients with tuberous sclerosis complex–associated renal angiomyolipoma: a descriptive study

Tuberous sclerosis complex (TSC) is a rare multisystem autosomal dominant genetic disease that occurs between 1 in 6,000 and 1 in 10,000 live births. Additionally, renal angiomyolipoma is the most common form of renal disease in patients affected by TSC. Although a genetic mutation analysis of TSC is not rare, the correlation between the TSC gene mutation and renal angiomyolipoma phenotype is poorly understood. This study aims to analyze the mutation sites in 261 types of selected TSC patients. The results reveal that: (1) female patients develop more renal angiomyolipoma than male patients [p = 0.008, OR = 2.474, 95%CI (1.258–4.864)]; (2). The missense mutation of TSC1 led to a higher risk of renal angiomyolipoma [p < 0.01, OR = 15, 95%CI (2.859–78.691)], and in contrast, showed a reduced risk in patients with frameshift mutation [p = 0.03, OR = 0.252, 95%CI (0.07–0.912)]; (3). Patients with TSC2 mutations in the transcription activation domain 1 coding genes, had increased renal angiomyolipoma [p = 0.019, OR = 3.519, 95%CI (1.226–10.101)]. Therefore, our genotype-phenotype correlation study might shed light on the early monitoring and evaluation of renal angiomyolipoma in TSC patients.

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Tuberous Sclerosis Complex: Genotype/Phenotype Correlation of Retinal Findings

Ophthalmology ◽

10.1016/j.ophtha.2012.03.020 ◽

2012 ◽

Vol 119 (9) ◽

pp. 1917-1923 ◽

Cited By ~ 50

Author(s):

Mary E. Aronow ◽

Jo Anne Nakagawa ◽

Ajay Gupta ◽

Elias I. Traboulsi ◽

Arun D. Singh

Keyword(s):

Tuberous Sclerosis ◽

Tuberous Sclerosis Complex ◽

Phenotype Correlation ◽

Genotype Phenotype Correlation

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High-throughput screening of circRNAs reveals novel mechanisms of tuberous sclerosis complex-related renal angiomyolipoma

Human Genomics ◽

10.1186/s40246-021-00344-1 ◽

2021 ◽

Vol 15 (1) ◽

Author(s):

Yang Zhao ◽

Hao Guo ◽

Wenda Wang ◽

Guoyang Zheng ◽

Zhan Wang ◽

...

Keyword(s):

Lipid Metabolism ◽

Tuberous Sclerosis ◽

Tuberous Sclerosis Complex ◽

Regulatory Network ◽

High Throughput Screening ◽

Kidney Tissue ◽

Cell Types ◽

The Body ◽

Differentially Expressed ◽

Renal Angiomyolipoma

Abstract Objective Tuberous sclerosis complex (TSC) is a rare autosomal dominant disease characterized by lesions throughout the body. Our previous study showed the abnormal up-regulation of miRNAs plays an important part in the pathogenesis of TSC-related renal angiomyolipoma (TSC-RAML). circRNAs were known as important regulators of miRNA, but little is known about the circRNAs in TSC-RAMLs. Methods Microarray chips and RNA sequencing were used to identify the circRNAs and mRNAs that were differently expressed between the TSC-RAML and normal kidney tissue. A competitive endogenous RNA (ceRNA) regulatory network was constructed to reveal the regulation of miRNAs and mRNAs by the circRNAs. The biological functions of circRNA and mRNA were analyzed by pathway analysis. Microenvironmental cell types were estimated with the MCP-counter package. Results We identified 491 differentially expressed circRNAs (DECs) and 212 differentially expressed genes (DEGs), and 6 DECs were further confirmed by q-PCR. A ceRNA regulatory network which included 6 DECs, 5 miRNAs, and 63 mRNAs was established. Lipid biosynthetic process was significantly up-regulated in TSC-RAML, and the humoral immune response and the leukocyte chemotaxis pathway were found to be down-regulated. Fibroblasts are enriched in TSC-RAML, and the up-regulation of circRNA_000799 and circRNA_025332 may be significantly correlated to the infiltration of the fibroblasts. Conclusion circRNAs may regulate the lipid metabolism of TSC-RAML by regulation of the miRNAs. Fibroblasts are enriched in TSC-RAMLs, and the population of fibroblast may be related to the alteration of circRNAs of TSC-RAML. Lipid metabolism in fibroblasts is a potential treatment target for TSC-RAML.

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Efficacy and Safety of Sirolimus for Renal Angiomyolipoma in Patients with Tuberous Sclerosis Complex or Sporadic Lymphangioleiomyomatosis: A Systematic Review

The Journal of Urology ◽

10.1016/j.juro.2014.04.096 ◽

2014 ◽

Vol 192 (5) ◽

pp. 1424-1430 ◽

Cited By ~ 23

Author(s):

Zhu-feng Peng ◽

Lu Yang ◽

Ting-ting Wang ◽

Ping Han ◽

Zhen-hua Liu ◽

...

Keyword(s):

Systematic Review ◽

Tuberous Sclerosis ◽

Tuberous Sclerosis Complex ◽

Renal Angiomyolipoma ◽

Efficacy And Safety

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RARE-25. RETINAL ASTROCYTOMA mTOR INHIBITOR THERAPY IN TUBEROUS SCLEROSIS MOSAICISM

Neuro-Oncology ◽

10.1093/neuonc/noaa222.736 ◽

2020 ◽

Vol 22 (Supplement_3) ◽

pp. iii447-iii447

Author(s):

Naomi Evans ◽

Katherine Paton ◽

Harinder Kaur Gill ◽

Juliette Hukin

Keyword(s):

Optic Nerve ◽

Retinal Detachment ◽

Tuberous Sclerosis ◽

Tuberous Sclerosis Complex ◽

Mtor Inhibitor ◽

Mammalian Target Of Rapamycin ◽

Neovascular Glaucoma ◽

Renal Angiomyolipoma ◽

Gradual Reduction ◽

Health Canada

Abstract INTRODUCTION Everolimus is an inhibitor of mTORC1 (mammalian target of rapamycin complex 1), it is Health Canada and FDA approved for SEGA and renal angiomyolipoma in the setting of tuberous sclerosis complex (TSC). There is little data available in regards to this treatment of TSC associated retinal astrocytoma (RA). Although the behaviour of RA is often indolent or slowly progressive, aggressive behaviour with retinal detachment and neovascular glaucoma requiring enucleation has been reported in several patients. Definite TSC diagnosis is established when either two major features or one major and two minor features are present. Probable TSC diagnosis is established when one major plus one minor feature is present. METHODS We report a child with probable TSC mosaicism, with negative serum NGS for TSC but RA and retinal achromic patch on the left. A left retinal peripapillary astrocytoma around optic nerve and very close to fovea was noted. There was concern that if it grew or there were to be any leakage it would cause visual impairment. This lead to therapy with everolimus 4.5 mg/m2/d aiming for level between 5 and 10 mcg/L. RESULTS This boy has had a gradual reduction of the RA over the last 29 months, with healthy retina in the region no longer occupied by the lesion and preserved vision. He has tolerated therapy well with occasional mouth ulcers. CONCLUSION mTORC1 inhibition is effective therapy to preserve vision in the setting of retinal astrocytoma and tuberous sclerosis mosaicism.

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