Fifty-three women pregnant with a fetus affected by cardiac tumor(s) were examined by standardized fetal echocardiography (FE), and fetuses, mothers and fathers, including other relevant family members if necessary, underwent familialTSC genetic testing.
Samples from fetuses (n = 13 after terminations) and newborns (n = 2) were available for targeted genomic sequencing of the exons and introns of the TSC1 and TSC2 genes and the adjacent 10 base pairs and for validated studies using Sanger sequencing.Among the 15 subjects with suspected cardiac rhabdomyoma and TSC genomic sequencing data, 7 subjects were familial and 8 subjects were sporadic cases.
In this study, we analyzed TSC1 and TSC2 in 57 Japanese patients with TSC (8 familial and 49 sporadic; 46 definite and 11 suspect TSC) and identified 31 mutations including 11 TSC1 mutations (two familial and nine sporadic; all definite TSC) and 20 TSC2 mutations (2 familial and 18 sporadic; 19 definite and 1 suspect TSC).
Although the majority of cases (65%) are sporadic, genetic linkage studies of familial cases led to the discovery of two separate genes linked to tuberous sclerosis complex: TSC1, located at chromosome 9q34, encoding a protein called hamartin; and TSC2, located at chromosome 16p13.3, encoding a protein called tuberin.
Mutations were identified in a total of 74 (59%) cases, including 16 TSC1 mutations (5 sporadic and 11 familial cases) and 58 TSC2 mutations (42 sporadic and 16 familial cases).
Here we report the first evidence of loss of heterozygosity at the TSC1 critical region in a giant cell astrocytoma of a familial tuberous sclerosis case.