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 gen e has been isolated, To date, only a small number of intragenic deleti onal and point mutations have been detected, almost exclusively in spo radic (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-Amer ican TSC family that shows a high likelihood for linkage to chromosome 16 ((z) over cap = 1.53), Using single-strand conformation polymorphi sm analysis we identified a 4590/4591 delC mutation in exon 34, The 45 90/4591delC causes a frameshift mutation resulting in the creation of a premature stop codon. In addition, we have detected a 5425del4 polym orphism in the two partially overlapping polyadenylation signals in ex on 40 that segregates in the family, The polymorphism has been detecte d in six of 72 African-American control chromosomes examined, and has not been detected in 80 Caucasian control chromosomes examined.