title: Geroderma osteodysplastica maps to a 4 Mb locus on chromosome 1q24.
abstract: Important insights into the etiology of osteoporosis have been gained by the study of single gene disorders, including osteogenesis imperfecta. We report on the genetic mapping of geroderma osteodysplastica (GO), a rare autosomal recessive disorder of the connective tissue, characterized by wrinkly skin and severe osteoporosis. We undertook autozygosity mapping in one Libyan and four consanguineous Pakistani families with a total of 10 affected individuals to define a 4 Mb homozygous region on chromosome 1q24, which harbors the GO causative gene. No obvious candidate genes that encode known protein constituents of the extracellular matrix are found in the linked region. Importantly, our study demonstrates that GO is not allelic to wrinkly skin syndrome caused by mutations in ATP6V0A2.
authors.affiliation: Academic Department of Medical Genetics, University of Manchester, and Regional Genetics Service, St Mary's Hospital, Manchester, UK. william.newman@manchester.ac.uk
authors.forename: William G
authors.initials: WG
authors.lastname: Newman
authors.forename: Jill
authors.initials: J
authors.lastname: Clayton-Smith
authors.forename: Kay
authors.initials: K
authors.lastname: Metcalfe
authors.forename: Rachel
authors.initials: R
authors.lastname: Cole
authors.forename: Marco
authors.initials: M
authors.lastname: Tartaglia
authors.forename: Francesco
authors.initials: F
authors.lastname: Brancati
authors.forename: Sara
authors.initials: S
authors.lastname: Morara
authors.forename: Antonio
authors.initials: A
authors.lastname: Novelli
authors.forename: Xiangdong
authors.initials: X
authors.lastname: Liu
authors.forename: Katherine A
authors.initials: KA
authors.lastname: Siminovitch
authors.forename: Stefan
authors.initials: S
authors.lastname: Mundlos
authors.forename: May
authors.initials: M
authors.lastname: Tassabehji
authors.forename: Graeme C M
authors.initials: GC
authors.lastname: Black
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics*; D003240:Connective Tissue Diseases / Q000235:genetics*; D003241:Consanguinity; D005260:Female; D005808:Genes, Recessive; D006801:Humans; D007223:Infant; D008002:Libya; D008297:Male; D018895:Microsatellite Repeats; D010024:Osteoporosis / Q000235:genetics*; D010154:Pakistan; D010375:Pedigree; D020161:Physical Chromosome Mapping; D006180:Proton-Translocating ATPases / Q000235:genetics; D015595:Skin Aging / Q000235:genetics; D012873:Skin Diseases, Genetic / Q000235:genetics*; D055815:Young Adult; D015053:Zygote
chemical_list: C525845:ATP6V0A2 protein, human; D006180:Proton-Translocating ATPases