title: A founder mutation for ichthyosis prematurity syndrome restricted to 76 kb by haplotype association.
abstract: Autosomal recessive congenital ichthyosis (ARCI) is a group of keratinisation disorders that includes the ichthyosis prematurity syndrome (IPS). IPS is rare and almost exclusively present in a restricted region in the middle of Norway and Sweden, which indicates a founder effect for the disorder. We recently reported linkage of IPS to chromosome 9q34, and we present here the subsequent fine-mapping of this region with known and novel microsatellite markers as well as single nucleotide polymorphisms (SNPs). Allelic association, evaluated with Fisher's exact test and P (excess), was used to refine the IPS haplotype to approximately 1.6 Mb. On the basis of the average length of the haplotype in IPS patients, we calculated the age of a founder mutation to approximately 1,900 years. The IPS haplotype contains a core region of 76 kb consisting of four marker alleles shared by 97.7% of the chromosomes associated with IPS. This region spans four known genes, all of which are expressed in mature epidermal cells. We present the results from the analysis of these four genes and their corresponding transcripts in normal and patient-derived samples.
authors.affiliation: Department of Genetics and Pathology, Rudbeck Laboratory, Uppsala University, Uppsala, 751 85, Sweden.
authors.forename: M
authors.initials: M
authors.lastname: Melin
authors.affiliation: Department of Genetics and Pathology, Rudbeck Laboratory, Uppsala University, Uppsala, 751 85, Sweden.
authors.forename: J
authors.initials: J
authors.lastname: Klar
authors.affiliation: Department of Dermatology, Rikshospitalet University Hospital, and Institute of Forensic Medicine, University of Oslo, Oslo, Norway.
authors.forename: T
authors.initials: T
authors.lastname: Jr Gedde-Dahl
authors.affiliation: Department of Neuroscience, Uppsala University, Uppsala, Sweden.
authors.forename: R
authors.initials: R
authors.lastname: Fredriksson
authors.affiliation: Department of Dermatology, University of Heidelberg, Heidelberg, Germany.
authors.forename: I
authors.initials: I
authors.lastname: Hausser
authors.affiliation: Department of Dermatology, Odense University Hospital, Odense, Denmark.
authors.forename: F
authors.initials: F
authors.lastname: Brandrup
authors.affiliation: Department of Dermatology, Odense University Hospital, Odense, Denmark.
authors.forename: A
authors.initials: A
authors.lastname: Bygum
authors.affiliation: Department of Medical Science, Uppsala University Hospital, Uppsala, Sweden.
authors.forename: A
authors.initials: A
authors.lastname: Vahlquist
authors.affiliation: Department of Genetics and Pathology, Rudbeck Laboratory, Uppsala University, Uppsala, 751 85, Sweden.
authors.forename: M
authors.initials: M
authors.lastname: Hellström Pigg
authors.affiliation: Department of Genetics and Pathology, Rudbeck Laboratory, Uppsala University, Uppsala, 751 85, Sweden. niklas.dahl@genpat.uu.se.
authors.forename: N
authors.initials: N
authors.lastname: Dahl
mesh_terms: D000483:Alleles; D002874:Chromosome Mapping; D002899:Chromosomes, Human, Pair 9; D004252:DNA Mutational Analysis; D018703:Founder Effect; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D007057:Ichthyosis / Q000235:genetics*; D008126:Lod Score; D018895:Microsatellite Repeats; D009154:Mutation; D009664:Norway; D020641:Polymorphism, Single Nucleotide; D013548:Sweden; D013577:Syndrome