title: Localization of one gene for tuberous sclerosis within 9q32-9q34, and further evidence for heterogeneity.
abstract: Tuberous sclerosis (TSC) is an autosomal dominant disorder with both neurological and cutaneous manifestations often resulting in significant disability. Although it has been studied clinically and biochemically for many years, the underlying pathophysiology remains unknown. Genetic linkage analysis provides an alternative strategy for understanding the genetic etiology of this disease. Genetic linkage of a gene for TSC to loci in 9q32-9q34 has been reported but has not been a universal finding, since absence of linkage to 9q loci, as well as linkage to loci on 11q, have also been reported. We present here data on 22 families (21 previously unreported) segregating TSC. Our results strongly support a TSC locus in the 9q32-34 region for approximately one-third of families and provide significant evidence for genetic heterogeneity. Application of newly described highly polymorphic dinucleotide repeat marker loci in TSC greatly enhanced the informativeness of our pedigrees and was vital for detecting the heterogeneity. No clear evidence of linkage to chromosome 11q22 markers was found, suggesting that a still unidentified TSC locus elsewhere in the genome may account for the majority of TSC families.
authors.affiliation: Molecular Neurogenetics Laboratory, Massachusetts General Hospital, Charlestown 02129.
authors.forename: J L
authors.initials: JL
authors.lastname: Haines
authors.forename: M P
authors.initials: MP
authors.lastname: Short
authors.forename: D J
authors.initials: DJ
authors.lastname: Kwiatkowski
authors.forename: A
authors.initials: A
authors.lastname: Jewell
authors.forename: E
authors.initials: E
authors.lastname: Andermann
authors.forename: B
authors.initials: B
authors.lastname: Bejjani
authors.forename: C H
authors.initials: CH
authors.lastname: Yang
authors.forename: J F
authors.initials: JF
authors.lastname: Gusella
authors.forename: J A
authors.initials: JA
authors.lastname: Amos
mesh_terms: D002899:Chromosomes, Human, Pair 9; D005260:Female; D005799:Genes, Dominant / Q000235:genetics*; D008040:Genetic Linkage / Q000235:genetics*; D005819:Genetic Markers / Q000235:genetics; D006579:Heterozygote; D006801:Humans; D008297:Male; D010375:Pedigree; D011110:Polymorphism, Genetic; D012091:Repetitive Sequences, Nucleic Acid; D014402:Tuberous Sclerosis / Q000235:genetics*
chemical_list: D005819:Genetic Markers