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Brain Symptoms of Tuberous Sclerosis Complex: Pathogenesis and Treatment
 
 
Article

Genotype and Phenotype Landscape of 283 Japanese Patients with Tuberous Sclerosis Complex

by 1,2,†, 1,2,†, 1 and 1,2,*
1
Center for Clinical Genomics, Kanazawa Medical University Hospital, Uchinada 920-0293, Japan
2
Department of Advanced Medicine, Division of Genomic Medicine, Medical Research Institute, Kanazawa Medical University, Uchinada 920-0293, Japan
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Academic Editor: Isidro Ferrer
Int. J. Mol. Sci. 2022, 23(19), 11175; https://doi.org/10.3390/ijms231911175
Received: 31 August 2022 / Revised: 16 September 2022 / Accepted: 19 September 2022 / Published: 22 September 2022
(This article belongs to the Special Issue New Molecular Insights into Neurocutaneous Syndromes)
Tuberous sclerosis complex (TSC) is an autosomal dominant disorder characterized by multiple dysplastic organ lesions and neuropsychiatric symptoms, caused by loss of function mutations in either TSC1 or TSC2. Genotype and phenotype analyses are conducted worldwide, but there have been few large-scale studies on Japanese patients, and there are still many unclear points. This study analyzed 283 Japanese patients with TSC (225 definite, 53 possible, and 5 genetic diagnoses). A total of 200 mutations (64 TSC1, 136 TSC2) were identified, of which 17 were mosaic mutations, 11 were large intragenic deletions, and four were splicing abnormalities due to deep intronic mutations. Several lesions and symptoms differed in prevalence and severity between TSC1 and TSC2 patients and were generally more severe in TSC2 patients. Moreover, TSC2 missense and in-frame mutations may attenuate skin and renal symptoms compared to other TSC2 mutations. Genetic testing revealed that approximately 20% of parents of a proband had mild TSC, which could have been missed. The patient demographics presented in this study revealed a high frequency of TSC1 patients and a low prevalence of epilepsy compared to global statistics. More patients with mild neuropsychiatric phenotypes were diagnosed in Japan, seemingly due to a higher utilization of brain imaging, and suggesting the possibility that a significant amount of mild TSC patients may not be correctly diagnosed worldwide. View Full-Text
Keywords: tuberous sclerosis complex; genotype–phenotype correlations; mutation detection methods; mosaic mutations; deep intronic mutations tuberous sclerosis complex; genotype–phenotype correlations; mutation detection methods; mosaic mutations; deep intronic mutations
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MDPI and ACS Style

Togi, S.; Ura, H.; Hatanaka, H.; Niida, Y. Genotype and Phenotype Landscape of 283 Japanese Patients with Tuberous Sclerosis Complex. Int. J. Mol. Sci. 2022, 23, 11175. https://doi.org/10.3390/ijms231911175

AMA Style

Togi S, Ura H, Hatanaka H, Niida Y. Genotype and Phenotype Landscape of 283 Japanese Patients with Tuberous Sclerosis Complex. International Journal of Molecular Sciences. 2022; 23(19):11175. https://doi.org/10.3390/ijms231911175

Chicago/Turabian Style

Togi, Sumihito, Hiroki Ura, Hisayo Hatanaka, and Yo Niida. 2022. "Genotype and Phenotype Landscape of 283 Japanese Patients with Tuberous Sclerosis Complex" International Journal of Molecular Sciences 23, no. 19: 11175. https://doi.org/10.3390/ijms231911175

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