title: Mutational analysis of paediatric patients with tuberous sclerosis complex in Korea: genotype and epilepsy.
abstract: To date, only a few studies have reported that, in tuberous sclerosis, TSC2 mutations are more frequently associated with infantile spasms and cognitive impairment compared to TSC1 mutations. We analyzed the mutational spectrum of patients with tuberous sclerosis in Korea and attempted to explore the associations between genotype and seizure type/outcome. We performed mutational analyses on 70 unrelated patients with clinically confirmed tuberous sclerosis by using direct DNA sequencing and/or multiplex ligation-dependent probe amplification. The patients' medical records, including epilepsy type and outcome, were reviewed retrospectively. We identified pathogenic mutations in 55 patients (79%), 25 of which were novel. There were 12 TSC1 mutations and 43 TSC2 mutations. TSC1 mutations included 8 frameshift and 4 nonsense mutations. TSC2 mutations included 12 frameshift, 10 nonsense, 6 splicing, and 6 missense mutations, as well as 4 in-frame deletions and 5 large deletions. Fifty-eight patients had epilepsy (83%), including 19 patients with a history of infantile spasms. Compared to patients with TSC1 mutations, individuals with TSC2 mutations had a significantly higher frequency of epilepsy (p<0.05) and tended to have a higher frequency of infantile spasms (37% vs 17%; p<0.3). Most of the patients with TSC2 mutations who developed infantile spasms exhibited subsequent epilepsy (13/14; 93%). However, the presence/absence of infantile spasms did not influence seizure remission or cognitive outcome.
authors.affiliation: Department of Pediatrics, Pediatric Clinical Neuroscience Center, Seoul National University Children's Hospital.
authors.forename: Jin Sook
authors.initials: JS
authors.lastname: Lee
authors.affiliation: Department of Pediatrics, Pediatric Clinical Neuroscience Center, Seoul National University Children's Hospital.
authors.forename: Byung Chan
authors.initials: BC
authors.lastname: Lim
authors.affiliation: Department of Pediatrics, Pediatric Clinical Neuroscience Center, Seoul National University Children's Hospital.
authors.forename: Jong-Hee
authors.initials: JH
authors.lastname: Chae
authors.affiliation: Department of Pediatrics, Pediatric Clinical Neuroscience Center, Seoul National University Children's Hospital.
authors.forename: Yong Seung
authors.initials: YS
authors.lastname: Hwang
authors.affiliation: Department of Laboratory Medicine, Seoul National University Hospital, Seoul, Korea.
authors.forename: Moon-Woo
authors.initials: MW
authors.lastname: Seong
authors.affiliation: Department of Laboratory Medicine, Seoul National University Hospital, Seoul, Korea.
authors.forename: Sung Sup
authors.initials: SS
authors.lastname: Park
authors.affiliation: Department of Pediatrics, Pediatric Clinical Neuroscience Center, Seoul National University Children's Hospital.
authors.forename: Ki Joong
authors.initials: KJ
authors.lastname: Kim
mesh_terms: D000293:Adolescent; D044466:Asian People / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D004827:Epilepsy / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D056910:Republic of Korea; D014402:Tuberous Sclerosis / Q000235:genetics*; D000077004:Tuberous Sclerosis Complex 1 Protein; D000077005:Tuberous Sclerosis Complex 2 Protein; D025521:Tumor Suppressor Proteins / Q000235:genetics*
chemical_list: C000624650:TSC1 protein, human; C000624653:TSC2 protein, human; D000077004:Tuberous Sclerosis Complex 1 Protein; D000077005:Tuberous Sclerosis Complex 2 Protein; D025521:Tumor Suppressor Proteins
keywords: TSC1; TSC2; genotype; outcome; seizure type; tuberous sclerosis complex