Infantile spasms and early-onset progressive polycystic renal lesions associated with TSC2/PKD1 contiguous gene deletion syndrome

Matsubara, Yoshie; Akamine, Satoshi; Chong, Pin Fee; Kawakami, Saori; Maehara, Kenji; Kaku, Yoshitsugu; Kurokawa, Mamoru; Morisada, Naoya; Iijima, Kazumoto; Kira, Ryutaro

doi:10.1016/j.seizure.2021.01.016

Cited by 2 publications

(1 citation statement)

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“…None of the four cases were accompanied by DD/ID, and two were a mother and her daughter, indicating that contiguous TSC2 / PKD1 deletion does not necessarily lead to severe neuropsychiatric symptoms. In the literature, there are reports of familial cases with mild neuropsychiatric symptoms [ 44 , 45 ] and cases with severe mental retardation [ 46 , 47 ]. Conversely, point mutations of TSC2 were detected in four out of eight patients with classic polycystic kidney disease ( Supplementary Table S1 ).…”

Section: Discussionmentioning

confidence: 99%

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

Togi

Ura

Hatanaka

et al. 2022

IJMS

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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.

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