title: Genetic heterogeneity in tuberous sclerosis.
abstract: Tuberous sclerosis (TSC) is an autosomal dominant disorder characterized by widespread hamartosis. Preliminary evidence of linkage between the TSC locus and markers on chromosome 9q34 was established, but subsequently disputed. More recently, a putative TSC locus on chromosome 11 has been suggested and genetic heterogeneity seems likely. Here we describe an approach combining multipoint linkage analysis and heterogeneity tests that has enabled us to obtain significant evidence for locus heterogeneity after studying a relatively small number of families. Our results support a model with two different loci independently causing the disease. One locus (TSC1) maps in the vicinity of the Abelson oncogene at 9q34 and a second locus (TSC2) maps in the region of the anonymous DNA marker Lam L7 and the dopamine D2 receptor gene at 11q23.
authors.affiliation: Department of Clinical Genetics, Academic Hospital Dijkzigt, The Netherlands.
authors.forename: L A
authors.initials: LA
authors.lastname: Janssen
authors.forename: L A
authors.initials: LA
authors.lastname: Sandkuyl
authors.forename: E C
authors.initials: EC
authors.lastname: Merkens
authors.forename: J A
authors.initials: JA
authors.lastname: Maat-Kievit
authors.forename: J R
authors.initials: JR
authors.lastname: Sampson
authors.forename: P
authors.initials: P
authors.lastname: Fleury
authors.forename: R C
authors.initials: RC
authors.lastname: Hennekam
authors.forename: G C
authors.initials: GC
authors.lastname: Grosveld
authors.forename: D
authors.initials: D
authors.lastname: Lindhout
authors.forename: D J
authors.initials: DJ
authors.lastname: Halley
mesh_terms: D002874:Chromosome Mapping; D002880:Chromosomes, Human, Pair 11; D005799:Genes, Dominant; D005819:Genetic Markers; D006801:Humans; D008126:Lod Score; D009857:Oncogenes; D010375:Pedigree; D012150:Polymorphism, Restriction Fragment Length; D014402:Tuberous Sclerosis / Q000235:genetics*
chemical_list: D005819:Genetic Markers