Dataset Information

Genotype and Phenotype Analysis of Chinese Children With Tuberous Sclerosis Complex: A Pediatric Cohort Study.

ABSTRACT: Tuberous sclerosis complex (TSC) is a genetic condition characterized by the occurrence of hamartomatous wounds stemming from the dysfunction of the mammalian target of rapamycin (mTOR) pathway. We investigated the clinical phenotypes and genetic variants in 243 unrelated probands and their families in China. Exome sequencing, targeted sequencing or multiplex ligation-dependent probe amplification (MLPA) was performed in 174 children with TSC, among whom 31 (17.82%) patients/families were identified as having pathogenic or likely pathogenic variants in the TSC1 gene, 120 (68.97%) as having pathogenic or likely pathogenic variants in the TSC2 gene and 23 (13.21%) as having no pathogenic or likely pathogenic variants identified (NMI). In the 31 patients with pathogenic or likely pathogenic TSC1 variants, 10 novel variants were detected among 26 different variants. In all 120 patients with TSC2 variants, 39 novel variants were found among a total of 107 different variants. We compared the phenotypes of the individuals with TSC1 pathogenic variants, TSC2 pathogenic variants and NMI. Patients with TSC2 variants were first diagnosed at a younger age (p = 0.003) and had more retinal hamartomas (p = 0.003) and facial angiofibromas (p = 0.027) (age ? 3 years) than individuals with TSC1 variants. Compared with individuals with TSC1/TSC2 pathogenic variants, NMI individuals had fewer cortical tubers (p = 0.003). Compared with individuals with TSC1 pathogenic variants, NMI patients had more retinal hamartomas (p = 0.035), and compared with individuals with TSC2 pathogenic variants, they had less epilepsy (p = 0.003) and fewer subependymal nodules (SENs) (p = 0.004).

SUBMITTER: Ding Y

PROVIDER: S-EPMC7076134 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Genotype and Phenotype Analysis of Chinese Children With Tuberous Sclerosis Complex: A Pediatric Cohort Study.

Ding Yifeng Y Wang Ji J Zhou Shuizhen S Zhou Yuanfeng Y Zhang Linmei L Yu Lifei L Wang Yi Y

Frontiers in genetics 20200310

Tuberous sclerosis complex (TSC) is a genetic condition characterized by the occurrence of hamartomatous wounds stemming from the dysfunction of the mammalian target of rapamycin (mTOR) pathway. We investigated the clinical phenotypes and genetic variants in 243 unrelated probands and their families in China. Exome sequencing, targeted sequencing or multiplex ligation-dependent probe amplification (MLPA) was performed in 174 children with TSC, among whom 31 (17.82%) patients/families were identi ...[more]

PMID: 32211034

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Project description:Background: Knowledge is increasing about TSC-Associated Neuropsychiatric Disorders (TAND), but little is known about the potentially confounding effects of intellectual ability (IA) on the rates of TAND across age, sex, and genotype. We evaluated TAND in (a) children vs. adults, (b) males vs. females, and (c) TSC1 vs. TSC2 mutations, after stratification for levels of IA, in a large, international cohort. Methods: Individuals of any age with a documented visit for TSC in the 12 months prior to enrolment were included. Frequency and percentages of baseline TAND manifestations were presented by categories of IA (no intellectual disability [ID, intelligence quotient (IQ)>70]; mild ID [IQ 50-70]; moderate-to-profound ID [IQ<50]). Chi-square tests were used to test associations between ID and TAND manifestations. The association between TAND and age (children vs. adults), sex (male vs. female), and genotype (TSC1 vs. TSC2) stratified by IA levels were examined using the Cochran-Mantel-Haenszel tests. Results: Eight hundred and ninety four of the 2,211 participants had formal IQ assessments. There was a significant association (P < 0.05) between levels of IA and the majority of TAND manifestations, except impulsivity (P = 0.12), overactivity (P = 0.26), mood swings (P = 0.08), hallucinations (P = 0.20), psychosis (P = 0.06), depressive disorder (P = 0.23), and anxiety disorder (P = 0.65). Once controlled for IA, children had higher rates of overactivity, but most behavioral difficulties were higher in adults. At the psychiatric level, attention deficit hyperactivity disorder (ADHD) was seen at higher rates in children while anxiety and depressive disorders were observed at higher rates in adults. Compared to females, males showed significantly higher rates of impulsivity and overactivity, as well as autism spectrum disorder (ASD) and ADHD. No significant age or sex differences were observed for academic difficulties or neuropsychological deficits. After controlling for IA no genotype-TAND associations were observed, except for higher rates of self-injury in individuals with TSC2 mutations. Conclusions: Findings suggest IA as risk marker for most TAND manifestations. We provide the first evidence of male preponderance of ASD and ADHD in individuals with TSC. The study also confirms the association between TSC2 and IA but, once controlling for IA, disproves the previously reported TSC2 association with ASD and with most other TAND manifestations.

Dataset Information

Genotype and Phenotype Analysis of Chinese Children With Tuberous Sclerosis Complex: A Pediatric Cohort Study.

Publications

Genotype and Phenotype Analysis of Chinese Children With Tuberous Sclerosis Complex: A Pediatric Cohort Study.

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