Novel TSC1 and TSC2 mutations in Japanese patients with tuberous sclerosis complex.
Tuberous sclerosis complex (TSC) is a neurocutaneous syndrome characterized by development of unusual tumor-like growths. Involvement of the brain is associated with the most problematic clinical manifestations of TSC, including intellectual retardation, epilepsy and abnormal behaviors. Until now, over 300 mutations of TSC1 and TSC2 were reported. Here, we report one novel mutation of TSC1 (Q897X) and five novel mutations of TSC2 (c.336+1 G>A, L345R, E700K, R905G, K914K) identified in Japanese patients with TSC. We also identified three new polymorphisms in TSC2 (N331N, A431A, S802G). The TSC1 mutation was predicted to cause a nonsense substitution whereas all of the five TSC2 mutations were predicted to cause either a splicing error or a missense substitution. In accordance with previous findings, the patients with TSC1 mutations had milder clinical manifestations than those with TSC2 mutations.
Yamamoto
Toshiyuki
T
Gene Research Center, Tottori University, Yonago 683-8503, Japan. tyamamot@grape.med.tottori-u.ac.jp
Pipo
Judy R
JR
Feng
Jian-Hua
JH
Takeda
Hiromasa
H
Nanba
Eiji
E
Ninomiya
Haruaki
H
Ohno
Kousaku
K
D000328:Adult; D002648:Child; D002675:Child, Preschool; D018389:Codon, Nonsense; D005091:Exons; D005260:Female; D006801:Humans; D007223:Infant; D007438:Introns; D007564:Japan; D008297:Male; D020125:Mutation, Missense; D011506:Proteins / Q000235:genetics*; D012097:Repressor Proteins / Q000235:genetics; D014402:Tuberous Sclerosis / Q000235:genetics*; D000077004:Tuberous Sclerosis Complex 1 Protein; D000077005:Tuberous Sclerosis Complex 2 Protein; D025521:Tumor Suppressor Proteins
D018389:Codon, Nonsense; D011506:Proteins; D012097:Repressor Proteins; C000624650:TSC1 protein, human; C000624653:TSC2 protein, human; D000077004:Tuberous Sclerosis Complex 1 Protein; D000077005:Tuberous Sclerosis Complex 2 Protein; D025521:Tumor Suppressor Proteins