Mutation analysis of the TSC2 gene in an African-American family.

Tuberous sclerosis complex is an autosomal dominant disorder with loci on chromosome 9q34 (TSC1) and chromosome 16p13.3 (TSC2). The TSC2 gene has been isolated. To date, only a small number of intragenic deletional and point mutations have been detected, almost exclusively in sporadic (no family history) cases. With the exception of a single parent/offspring pair, there have been no published reports of mutations in extended multigenerational chromosome 16-linked TSC2 families. For our TSC studies we ascertained and sampled a four-generation African-American TSC family that shows a high likelihood for linkage to chromosome 16 (z=1.53). Using single-strand conformation polymorphism analysis we identified a 4590/4591delC mutation in exon 34. The 4590/4591delC causes a frameshift mutation resulting in the creation of a premature stop codon. In addition, we have detected a 542del4 polymorphism in the two partially overlapping polyadenylation signals in exon 40 that segregates in the family. The polymorphism has been detected in six of 72 African-American control chromosomes examined, and has not been detected in 80 Caucasian control chromosomes examined.