[P2-161] Relationship between various clinical features in a genotyped population investigated for tuberous sclerosis complex
[Introduction] Tuberous Sclerosis Complex (TSC) is a multi-system disorder, typically involving severe neurological symptoms, severe cutaneous manifestation, and various tumors, such as subependymal giant cell astrocytoma (SEGA), renal angiomyolipoma (rAML) and lung lymphangioleiomyomatosis and/or multifocal micronodular pneumocyte hyperplasia (LAM/MMPH). TSC is inherited in an autosomal dominant pattern and is caused by mutations in either the TSC1 or TSC2 genes, which enhance activation of the mammalian target of rapamycin (mTOR) signaling pathway. In this study, we investigated patients with various TSC manifestations to reveal the difference with genotype.
[Patients and Methods] We retrospectively investigated in a cohort of TSC outpatients of Fujita Health University Hospital, clinical manifestations and genetic mutations. Twenty-one patients who were diagnosed as TSC clinically underwent genetic testing.
[Results] Clinical manifestations of 21 patients were following; 19 patients with epilepsy, 14 with rAML, 11 with LAM/MMPH, and 6 with SEGA. Eighteen patients had mutations in TSC2 gene, and three had in TSC1 gene. Mutations were following; 5 patients with nonsense mutation, 10 with frameshift mutation, 2 with missense mutation, and the rest one by one with one amino acid deletion, splice site mutation and deletion of exons. One patient had concomitant PDK1 deletion in which led to contiguous gene syndrome.
[Conclusions] In our cohort, many of them have epilepsy and rAML, and have TSC2 truncated mutations, indicating that the TSC2 truncated mutation is linked to much severe clinical manifestations. Early pharmacotherapy interventions based on genotype may be available for our TSC patients.
[Patients and Methods] We retrospectively investigated in a cohort of TSC outpatients of Fujita Health University Hospital, clinical manifestations and genetic mutations. Twenty-one patients who were diagnosed as TSC clinically underwent genetic testing.
[Results] Clinical manifestations of 21 patients were following; 19 patients with epilepsy, 14 with rAML, 11 with LAM/MMPH, and 6 with SEGA. Eighteen patients had mutations in TSC2 gene, and three had in TSC1 gene. Mutations were following; 5 patients with nonsense mutation, 10 with frameshift mutation, 2 with missense mutation, and the rest one by one with one amino acid deletion, splice site mutation and deletion of exons. One patient had concomitant PDK1 deletion in which led to contiguous gene syndrome.
[Conclusions] In our cohort, many of them have epilepsy and rAML, and have TSC2 truncated mutations, indicating that the TSC2 truncated mutation is linked to much severe clinical manifestations. Early pharmacotherapy interventions based on genotype may be available for our TSC patients.