title: A third gene locus for tuberous sclerosis is closely linked to the phenylalanine hydroxylase gene locus.
abstract: Following the observation of a patient suffering from tuberous sclerosis (TSC) with a de novo reciprocal translocation t(3;12) (p26.3;q23.3), we have undertaken a linkage study in 15 TSC families using polymorphic DNA markers neighbouring the chromosome breakpoints. Significant lod scores have been obtained for markers D12S7 (Zmax = 2.34, theta = 0.14) and PAH (phenylalanine hydroxylase (Zmax = 4.34, theta = 0.0). In multipoint linkage analysis, the peak lod score was 4.56 at the PAH gene locus. These data suggest the existence of a third gene locus for TSC (TSC3) on chromosome 12q22-24.1. The regions that have been found to be linked to TSC in different families map to the positions of three enzymes, phenylalanine hydroxylase (12q22-24), tyrosinase (11q14-22), and dopamine-beta-hydroxylase (9q34), all of which are involved in the conversion of phenylalanine to catecholamine neurotransmitters or melanin. Disorders of these biochemical pathways might be involved in the pathogenesis of TSC.
authors.affiliation: Institut für Humangenetik, Universität Erlangen-Nürnberg, Federal Republic of Germany.
authors.forename: R
authors.initials: R
authors.lastname: Fahsold
authors.forename: H D
authors.initials: HD
authors.lastname: Rott
authors.forename: P
authors.initials: P
authors.lastname: Lorenz
mesh_terms: D002880:Chromosomes, Human, Pair 11; D002881:Chromosomes, Human, Pair 12; D002899:Chromosomes, Human, Pair 9; D005260:Female; D008040:Genetic Linkage; D006801:Humans; D008126:Lod Score; D008297:Male; D010375:Pedigree; D010651:Phenylalanine Hydroxylase / Q000235:genetics*; D014402:Tuberous Sclerosis / Q000235:genetics*
chemical_list: D010651:Phenylalanine Hydroxylase