Genetics, genomics, and genotype–phenotype correlations of TSC: Insights for clinical practice

Peron, Angela; Au, Kit Sing; Northrup, Hope

doi:10.1002/ajmg.c.31651

Cited by 72 publications

(72 citation statements)

References 62 publications

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“…It was reported that TSC2 gene mutations are more common than TSC1 gene mutations (Peron et al, 2018a(Peron et al, , 2018b and that they are associated with an increased risk of seizures (Dabora et al, 2001). The fact that our patients had intractable epilepsy may partially account for our finding more TSC2 gene mutations than TSC1 gene mutations in our cohort.…”

Section: Discussionmentioning

confidence: 53%

TSC1 and TSC2 Gene Mutations in Chinese Tuberous Sclerosis Complex Patients Clinically Characterized by Epilepsy

Zhou

Shi

et al. 2020

Genetic Testing and Molecular Biomarkers

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Tuberous sclerosis complex (TSC) is a multisystem disease. Variants in the TSC1 and TSC2 genes have been reported to be associated with TSC and are considered pathogenic. The purpose of this study was to determine the genetic mutations and expression patterns of TSC1 and TSC2 in 21 Chinese patients suffering from TSC who were clinically characterized by epilepsy. Methods: Peripheral blood samples were taken from 21 patients, their parents, and other family members. Their TSC1 and TSC2 genes were sequenced through next-generation sequencing to identify all variants. Results: We identified variants in 17/21 patients in either their TSC1 or TSC2 genes: 6 patients had TSC1 mutations and 11 had TSC2 mutations. There were 13 spontaneous mutations, and 3 that had been inherited from a parent. The mutations were classified by types: there were three missense mutations, five frameshift mutations, two splice site mutations, four nonsense mutations, two single codon deletions resulting the loss of an amino acid, and one large fragment deletion. Six of the mutations have not been previously reported. Conclusion: The genotypic analysis of Chinese TSC patients who are clinically characterized by epilepsy can potentially be useful for genetic counseling and prenatal diagnoses for patients and their families.

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Section: Discussionmentioning

confidence: 53%

TSC1 and TSC2 Gene Mutations in Chinese Tuberous Sclerosis Complex Patients Clinically Characterized by Epilepsy

Zhou

Shi

et al. 2020

Genetic Testing and Molecular Biomarkers

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“…TSC2 mutations are usually related to a more severe phenotype than that in TSC1 mutations [20] . The ratio of TSC1 mutations in our study is lower than reported, and this may due to more patients with TSC1 mutations had milder phenotypes and patients with TSC2 mutations were more likely to seek treatment.…”

Section: Discussionmentioning

confidence: 99%

Analysis of renal lesions in Chinese tuberous sclerosis complex patients with different conditions of TSC1/2 genetic mutations

Wang¹,

Zhao²,

Wang³

et al. 2020

Preprint

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Objective The renal manifestations of tuberous sclerosis complex (TSC) are complicated and various. We’d like to report the information of genetic mutations in TSC patients with renal lesions, and to discuss the relationship between features of renal lesions and genetic mutations, including mutant genes and mutant types. Methods TSC patients with renal lesions who came to Urology Department of our hospital from January 1st, 2015 to January 1st, 2020 were retrospectively analyzed. TSC patients who received next generation sequencing (NGS) of TSC1/2 and imaging examinations were screened out. When familial TSC patients were confirmed, only the probands were included. The patients who had imaging evaluation in our hospital before any treatment for TSC renal angiomyolipomas (AMLs) were also selected for further analysis of relationship between genetic mutations and AML sizes. Results 70 clinically or genetically diagnosed TSC patients with renal lesions were included. The average age was 29.3±8.3 years old. Male-female ratio was 1:1.5. 15 patients (21.4%) were probands of TSC families (3 TSC1 , 10 TSC2 , and 2 NMI). 67 patients (95.8%) had bilateral renal AMLs with one patient had a pathological diagnosis of epithelioid AML ( TSC2 mutation). One patient had multiple renal cysts ( TSC2 mutation), one had renal cell carcinomas (RCCs) ( TSC1 mutation) and one had Wilms tumors ( TSC1 mutation). Among the 70 included patients, 4 patients had TSC1 mutations, 51 had TSC2 mutations, and 15 had no mutation identified (NMI). There was no statistically significant difference between TSC2 mutations and NMI groups (11.4±5.7 vs. 8.0±5.6cm, P = 0.077) when considering AML sizes. There was also no statistically significant difference among AML sizes of patients with TSC2 mutation types of nonsense, missense, frameshift, slipping, and fragment deletion ( P = 0.712). And no statistically significant difference was found between maximus diameters in familial and sporadic patients, either (11.4±5.8 vs. 10.5±5.8, P = 0.663). Conclusions The conditions of TSC genetic mutations will affect type and severity of renal lesions. Other focuses such as protein structure and function need to be studied for renal manifestations. Except for patients with TSC1 and TSC2 genetic mutations, patients with NMI and familial patients are also needed more attention for the pathogenesis of them is still unknown.

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“…Die Diagnose kann häufig anhand klinischer Kriterien gestellt werden [118], aber die Präsentation ist sehr variabel. Eine genetische Diagnostik ist zu empfehlen, wenn die Diagnose klinisch nicht eindeutig ist (besonders bei jüngeren Kindern), oder eine Relevanz zur genetischen Beratung weiterer Familienangehöriger besteht [119]. Nierenzysten sind nur ein Minor-Kriterium bei der klinischen Diagnose, ≥ 2 Angiomyolipome aber ein Major-Kriterium [118].…”

Section: Tuberöse Skleroseunclassified

Nierenzysten und zystische Nierenerkrankungen bei Kindern (AWMF S2k-Leitlinie)

et al. 2020

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ZusammenfassungDie Leitlinie wurde im Konsens aller relevanten deutschen Fachgesellschaften zusammen mit Patientenvertretern erstellt. Standard der prä- und postnatalen Bildgebung von Nierenzysten ist die Sonografie, die auch im Abdomen und inneren Genitale extrarenale Manifestationen ausschließen soll. Die MRT hat einzelne Indikationen. Bei Verdacht auf zystische Nierenerkrankungen ist eine kindernephrologische Vorstellung indiziert. Die pränatale Betreuung muss auf sehr unterschiedliche Schweregrade zugeschnitten werden. Bei renalem Oligohydramnion wird eine Entbindung in einem Perinatalzentrum der höchsten Stufe empfohlen. Neugeborenen sollte eine Nierenersatztherapie nicht allein aufgrund des Alters vorenthalten werden. Bei unilateraler multizystischer Nierendysplasie ist keine funktionelle Bildgebung oder Nephrektomie notwendig, aber (wie auch bei uni- oder bilateraler Nierenhypo-/dysplasie mit Zysten) eine langfristige nephrologische Überwachung. Bei der ARPKD (autosomal rezessive polyzystische Nierenerkrankung), Nephronophthise, Bardet-Biedl-Syndrom und HNF1B-Mutationen müssen extrarenale Manifestationen beachtet werden; eine genetische Testung ist hier sinnvoll. Kinder mit tuberöser Sklerose, Tumorprädispositionen (z. B. von Hippel Lindau Syndrom) oder hohem Risiko für erworbene Nierenzysten sollten regelmäßige Nierensonografien erhalten. Auch asymptomatische Kinder von Eltern mit ADPKD (aut. dominanter polyzystischer Nierenerkrankung) sollten regelmäßig auf Hypertonie und Proteinurie untersucht werden. Eine präsymptomatische sonografische oder genetische Diagnostik dieser Minderjährigen sollte nur nach ausführlicher Aufklärung erwogen werden. Einfache (isolierte) Zysten sind bei Kindern sehr selten und eine ADPKD eines Elternteils sollte ausgeschlossen sein. Komplexe Nierenzysten bedürfen weiterer Abklärung.

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Genetics, genomics, and genotype–phenotype correlations of TSC: Insights for clinical practice

Cited by 72 publications

References 62 publications

TSC1 and TSC2 Gene Mutations in Chinese Tuberous Sclerosis Complex Patients Clinically Characterized by Epilepsy

TSC1 and TSC2 Gene Mutations in Chinese Tuberous Sclerosis Complex Patients Clinically Characterized by Epilepsy

Analysis of renal lesions in Chinese tuberous sclerosis complex patients with different conditions of TSC1/2 genetic mutations

Nierenzysten und zystische Nierenerkrankungen bei Kindern (AWMF S2k-Leitlinie)

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