title: [Novel TSC1 mutation associated with variable phenotypes in tuberous sclerosis].
abstract: Tuberous sclerosis is an autosomal dominant disorder, caused by mutations of the TSC1 or TSC2 genes resulting in tumor predisposition. Clinical signs include non-malignant brain tumors, skin, eye, heart and kidney abnormalities. The authors report a Hungarian family with broad phenotypic variability. First, the 5-year-old boy, showing the most symptoms was examined, whose first seizure occurred at 15 months and a cranial magnetic resonance imaging revealed numerous intracerebral calcareous foci. Except of hypopigmented skin spots, no other abnormality was found on physical examination. The mother was completely asymptomatic. Epilepsy of the maternal uncle started at the age of 3 years, of his sister at the age of 17 years and of the maternal grandmother at the age of 39 years. At the age of 52 years the grandmother developed renal cysts. Molecular genetic analysis of the family confirmed a de novo heterozygous point mutation (c.2524 C\>T) [corrected] in exon 20 of the TSC1 gene. The mutation was detected in all examined family members. Despite increasing data on the pathomechanism of tuberous sclerosis, there is still little known about the genetic modifying factors influencing the broad intra- and interfamilial phenotypic variability.
authors.affiliation: Pécsi Tudományegyetem Klinikai Központ, Orvosi Genetikai Intézet Pécs Szigeti út 12. 7623 Pécsi Tudományegyetem, Általános Orvostudomáyi Kar, Szentágothai Kutatóközpont, Pécs. kovesdi.erzsebet@ptc.hu
authors.forename: Erzsébet
authors.initials: E
authors.lastname: Kövesdi
authors.forename: Kinga
authors.initials: K
authors.lastname: Hadzsiev
authors.forename: Katalin
authors.initials: K
authors.lastname: Komlósi
authors.forename: Mária
authors.initials: M
authors.lastname: Kassay
authors.forename: Péter
authors.initials: P
authors.lastname: Barsi
authors.forename: Béla
authors.initials: B
authors.lastname: Melegh
mesh_terms: D001483:Base Sequence; D002675:Child, Preschool; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D012640:Seizures / Q000235:genetics; D014402:Tuberous Sclerosis / Q000175:diagnosis* / Q000235:genetics*; D000077004:Tuberous Sclerosis Complex 1 Protein; D025521:Tumor Suppressor Proteins / Q000235:genetics*
chemical_list: C000624650:TSC1 protein, human; D000077004:Tuberous Sclerosis Complex 1 Protein; D025521:Tumor Suppressor Proteins