title: Mutation analysis of the TSC2 gene in an African-American family.
abstract: 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.
authors.affiliation: Division of Neurology, Duke Unversity Medical Center, Durham, NC 27710, USA.
authors.forename: A
authors.initials: A
authors.lastname: Kumar
authors.forename: R S
authors.initials: RS
authors.lastname: Kandt
authors.forename: C
authors.initials: C
authors.lastname: Wolpert
authors.forename: A D
authors.initials: AD
authors.lastname: Roses
authors.forename: M A
authors.initials: MA
authors.lastname: Pericak-Vance
authors.forename: J R
authors.initials: JR
authors.lastname: Gilbert
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D044383:Black People / Q000235:genetics*; D002885:Chromosomes, Human, Pair 16; D004247:DNA; D005091:Exons; D005260:Female; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D010375:Pedigree; D011110:Polymorphism, Genetic; D012097:Repressor Proteins / Q000235:genetics*; D017384:Sequence Deletion; D013728:Terminator Regions, Genetic; D014402:Tuberous Sclerosis / Q000208:ethnology / Q000235:genetics*; D000077005:Tuberous Sclerosis Complex 2 Protein; D025521:Tumor Suppressor Proteins; D001741:Black or African American
chemical_list: D012097:Repressor Proteins; C000624653:TSC2 protein, human; D000077005:Tuberous Sclerosis Complex 2 Protein; D025521:Tumor Suppressor Proteins; D004247:DNA