Genotype/phenotype correlation in 123 Chinese patients with Tuberous Sclerosis Complex

Luk, Ho‐Ming; Hau, Edgar W L; Cheng, Shirley SW.; Yu, Kris PT.; Ho, Stephanie; Mok, Myth TS.; Lo, Ivan F. M.

doi:10.1016/j.ejmg.2022.104573

Cited by 4 publications

(4 citation statements)

References 29 publications

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“…Regarding hotspots, the highest proportion of pathogenic variants was identi ed in exons 15 and 18 for TSC1 and in exons 34, 35, and 41 for TSC2. Exon 15 is the largest exon in TSC1, which explains why it has been found to be a hotspot in several cohorts [3,10,27,31,35]. Exons 15 and 18 of TSC1 are located within the coiled-coil domain, and exon 18 was highlighted as a hotspot in a Mexican cohort study by Reyna-Fabian et al [31].…”

Section: Discussionmentioning

confidence: 99%

“…For TSC2, IESS was signi cantly more prevalent in the middle mutation domain (exons [23][24][25][26][27][28][29][30][31][32][33] than in the hamartin domain. Additionally, the middle mutation domain showed a higher incidence of refractory epilepsy than other domains, although the difference was not statistically signi cant.…”

Section: Discussionmentioning

confidence: 99%

“…For TSC2, the hotspots were identi ed in exon 34, 35, and 41, which are all located in the GAP domain. Various exons within the GAP domain of TSC2 have been reported as hotspots, including exons 35-41 [10,27,31,35]. Ding et al indicated a higher density of variants in the functional domain regions of TSC2 than in TSC1 [11].…”

Section: Discussionmentioning

confidence: 99%

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Genotypic and Phenotypic Analysis of Korean Patients with Tuberous Sclerosis

Shin,

Lee,

Kim

et al. 2024

Preprint

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Tuberous sclerosis complex (TSC) is a rare autosomal dominant disorder caused by mutations in the TSC1 or TSC2 gene. The aim of this study was to analyze the genotypes and phenotypes of Korean patients diagnosed with TSC and expand our understanding of this disorder. This retrospective observational study included 331 patients clinically diagnosed with TSC between November 1990 and April 2023 at Severance Children’s Hospital, Seoul, South Korea. The demographic and clinical characteristics of the patients were investigated. Twenty-five novel variants were identified. Of the 331 patients, 188 underwent genetic testing, and genotype-phenotype variation was analyzed according to the type of gene mutation and functional domain. Fifty-one patients (51/188, 27%) were had TSC1 mutations, 109 (58%) had TSC2 mutations, and 28 (8.5%) had no mutation identified (NMI). Hotspots were identified in exons 15 and 18 of TSC1 and exons 34, 35, and 41 of TSC2. Patients with TSC2 mutations exhibited a significantly younger age at the time of seizure onset and had refractory epilepsy. Infantile epileptic spasms syndrome (IESS) was more common in the middle mutation domain of TSC2 than in the hamartin domain (p = 0.047). Additionally, retinal hamartoma, cardiac rhabdomyoma, and renal abnormalities were significantly associated with TSC2 compared with other gene types. This study contributes to our understanding of TSC by expanding the genotypic spectrum with novel variants and providing insights into the clinical spectrum of patients with TSC in Korea.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Genotypic and Phenotypic Analysis of Korean Patients with Tuberous Sclerosis

Shin,

Lee,

Kim

et al. 2024

Preprint

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“…1 The main genetic mechanism includes mutations in tuberous sclerosis 1 and 2 genes (TSC1 and TSC2) gene locus responsible for encoding hamartin and tuberin protein, what leads to overactivation of mTOR pathway and finally leads to the growth of hamartomas in multiple organs, what is main pathological base of clinical presentations. 2 The main clinical presentations include different neurological symptoms usually presented with cognitive and behavioural disorders. Epilepsy is the most prevalent and clinically important manifestation of tuberous sclerosis, with wide range of clinical presentation from infantile spasms to refractory epilepsy.…”

Section: Introductionmentioning

confidence: 99%

Neurological manifestations of tuberous sclerosis are more common in patients with earlier stages than in the end stage of the chronic kidney disease: Multicentric study from South-Eastern Europe countries

Prelević

Juric

Bilić

et al. 2022

Journal of Global Health Neurology and Psychiatry

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Background Tuberous sclerosis is a rare, genetic disease with the various clinical presentations with most frequent clinical presentation which includes epileptic seizures and cognitive disorders. The main cause of mortality in those group of patients is renal impairment., and in some cases, neurological and renal clinical manifestation can be followed, but can also be the main therapeutic aim of mTOR inhibitors. Here, we aimed to correlate neurological symptoms with different stages of chronic kidney disease. Methods This multicentric retrospective study included 51 patients from clinical centres from seven South-Eastern Europe countries We included patients older then 18 years with possible or definitive diagnosis of TSC. Data were collected from nephrological and neurological registries form clinical centres. Results Study enrolled 51 patients with a median age of 32.3 years and predominant female gender. Neurological symptoms represented with epiletic sizures were more common in patients in earlier stages of CKD (nonESRD patients) then in patients in the end-stage renal disease. Conclusion Results of this study have shown that neurological manifestation in analyzed cohort correlate with renal lesions in early stage of chronic kidney disease.

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