Quick genetic screening using targeted next-generation sequencing in patients with tuberous sclerosis.
Tuberous sclerosis complex is an autosomal dominant disorder characterized by hamartomas in multiple organ systems. Mutations in the 2 large genes TSC1 and TSC2 have been demonstrated to be associated with tuberous sclerosis complex by various mutation screening methods. Targeted next-generation sequencing for genetic analysis is performed in the current study and is proved to be less cost, labor, and time consuming compared with Sanger sequencing. Two de novo and 1 recurrent TSC2 mutation in patients with tuberous sclerosis complex were revealed. Clinical details of patients were described and the underlying mechanism of the 2 novel TSC2 mutations, c.245G>A(p.W82X) and c.5405_5408dupACTT(p.P1803Lfs*25), were discussed. These results added to variability of TSC mutation spectrum and suggest that targeted next-generation sequencing could be the primary choice over Sanger sequencing in future tuberous sclerosis complex genetic counseling.
Department of Neurology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College (CAMS & PUMCH), Beijing, China.
Qing
Q
Liu
Department of Neurology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College (CAMS & PUMCH), Beijing, China.
Yan
Y
Huang
Beijing Genomics Institute at Shenzhen, Shen Zhen, China.
Mingrong
M
Zhang
State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, CAMS & PUMCH, Beijing, China.
Lian Qing
LQ
Wang
State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, CAMS & PUMCH, Beijing, China.
Xia Nan
XN
Guo
State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, CAMS & PUMCH, Beijing, China.
Nuo
N
Si
State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, CAMS & PUMCH, Beijing, China.
Zhan
Z
Qi
Department of Neurology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College (CAMS & PUMCH), Beijing, China zhouwangxq@126.com.
Xiang Qin
XQ
Zhou
Department of Neurology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College (CAMS & PUMCH), Beijing, China.
Li-ying
LY
Cui
D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis / Q000379:methods*; D005260:Female; D005820:Genetic Testing / Q000379:methods*; D006801:Humans; D008297:Male; D009154:Mutation; D012333:RNA, Messenger; D014402:Tuberous Sclerosis / Q000175:diagnosis / Q000235:genetics*; D000077005:Tuberous Sclerosis Complex 2 Protein; D025521:Tumor Suppressor Proteins / Q000235:genetics
D012333:RNA, Messenger; C000624653:TSC2 protein, human; D000077005:Tuberous Sclerosis Complex 2 Protein; D025521:Tumor Suppressor Proteins
Sanger sequencing; messenger RNA decay; mutation; next-generation sequencing; tuberous sclerosis complex