The Correlation Between Tuberous Sclerosis Complex Genotype and Renal Angiomyolipoma Phenotype

Abstract

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.

Angiomyolipoma of Uterine Cervix: Report of a Rare Case

“…AML is commonly associated with tuberous sclerosis (TSC), and renal AML is the most common manifestation of renal disease in patients with TSC. Mutations in TSC1 and TSC2 genes increase the risk of developing renal AML [ 12 - 13 ]. Association with sporadic lymphangioleiomyomatosis (LAM) in 60% was seen [ 16 ].…”

“…The malignant variant of angiomyolipoma is known as epithelioid angiomyolipoma (EAML), rarely encountered within the kidney [ 11 ]. Mutations in TSC1 and TSC2 genes increase the risk of developing renal AML [ 12 - 13 ]. Large tumors can present with symptoms of abnormal vaginal bleeding, pelvic pain, and abdominal bloating, and most small-sized tumors are asymptomatic [ 14 ].…”

A multi‑omics study of diagnostic markers and the unique inflammatory tumor micro‑environment involved in tuberous sclerosis complex‑related renal angiomyolipoma

“…Although a large number of studies have focused on genotype-phenotype correlation, no definite conclusion regarding TSC-RAML has been made, unless the TSC2 mutation is much more severe than that of TSC1 ( 27 , 28 , 46 , 47 ). A relatively large systematic review including 261 patients with TSC suggested that TSC1 missense mutation and the mutation of TSC2 encoding TAD1 were associated with a high risk of TSC-RAML ( 28 ). The present study attempted to find the proteins associated with phenotype.…”

“…3A and B suggest that the existence of LAM does not appear to influence the plasma proteomics because among the 903 proteins, only 16 pretreatment and 17 post-treatment molecules were statistically significant. It has been proposed that TSC2 gene mutation and those producing premature termination codons may lead to a severe phenotype (27,28). For plasma proteomics, it appears that a TSC2 mutation prior to treatment has a substantial influence on patients with 31 DEPs and S100 family members, such as S100A6, -A9 and -A12, had a tendency to be upregulated among patients with TSC2 mutation, which has been proved to engage in the neutrophil and macrophage accumulation, corresponding cytokine secretion and smooth muscle cell proliferation (29)(30)(31)(32).…”

Renal phenotypes correlate with genotypes in unrelated individuals with tuberous sclerosis complex in China

“…While another Chinese cohort study found that the renal AML volume of TSC2 variants was significantly larger than that of TSC1 variants [ 28 ]. More recently, the correlation between mutational sites and renal AML have been evaluated [ 29 ]. It identified some mutational sites, such as TSC2 mutations in the transcription activation domain 1 coding genes, had higher risk of renal AML.…”