title: Novel mutation in the TSC2 gene associated with prenatally diagnosed cardiac rhabdomyomas and cerebral tuberous sclerosis.
abstract: Cardiac rhabdomyomas are prenatal echocardiographic markers for tuberous sclerosis complex (TSC). TSC is caused by mutations in the genes TSC1 and TSC2. We report a 28-year-old, gravida 5, para 2, woman with an uncomplicated pregnancy until prenatal ultrasound at 34 weeks' gestation revealed fetal cardiac tumors. Ultrafast magnetic resonance imaging (MRI) at 36 weeks' gestation showed cardiac rhabdomyomas and small subependymal tubers. At 39 weeks' gestation, a 2,262 g female infant was delivered uneventfully. Postnatal echocardiography confirmed cardiac rhabdomyomas and MRI verified small cerebral subependymal tubers. Mutational analysis of TSC1 and TSC2 genes using denaturing high-performance liquid chromatography and direct sequencing of the genes was performed and revealed that the parents had wildtype DNA, while the proband was heterozygous for a novel de novo nonsense mutation, c.4830G >A, in exon 36 of the TSC2 gene, resulting in a change of codon 1610 TGG (tryptophan) to TGA (stop codon). The mutation predicted a W1610X premature termination of the tuberin protein. These findings support an association between a TSC2 de novo nonsense mutation and prenatally detected cardiac rhabdomyomas and cerebral tuberous sclerosis. Familial molecular analysis of TSC1 and TSC2 in cases with prenatally diagnosed cardiac rhabdomyomas and cerebral tuberous sclerosis lesions is helpful in prenatal diagnosis and genetic counseling.
authors.affiliation: Department of Obstetrics and Gynecology, Mackay Memorial Hospital, Institute of Clinical Nursing, School of Nursing, National Yang-Ming University, Taipei, Taiwan. cpc_mmh@yahoo.com
authors.forename: Chih-Ping
authors.initials: CP
authors.lastname: Chen
authors.forename: Yi-Ning
authors.initials: YN
authors.lastname: Su
authors.forename: Chia-Cheng
authors.initials: CC
authors.lastname: Hung
authors.forename: Jin-Chung
authors.initials: JC
authors.lastname: Shih
authors.forename: Wayseen
authors.initials: W
authors.lastname: Wang
mesh_terms: D000328:Adult; D001927:Brain Diseases / Q000175:diagnosis / Q000235:genetics*; D002851:Chromatography, High Pressure Liquid; D018389:Codon, Nonsense; D005260:Female; D006338:Heart Neoplasms / Q000175:diagnosis / Q000235:genetics*; D006801:Humans; D011247:Pregnancy; D011296:Prenatal Diagnosis; D012207:Rhabdomyoma / Q000175:diagnosis / Q000235:genetics*; D014402:Tuberous Sclerosis / Q000175:diagnosis / Q000235:genetics*; D000077004:Tuberous Sclerosis Complex 1 Protein; D000077005:Tuberous Sclerosis Complex 2 Protein; D025521:Tumor Suppressor Proteins / Q000235:genetics*
chemical_list: D018389:Codon, Nonsense; C000624650:TSC1 protein, human; C000624653:TSC2 protein, human; D000077004:Tuberous Sclerosis Complex 1 Protein; D000077005:Tuberous Sclerosis Complex 2 Protein; D025521:Tumor Suppressor Proteins