title: The novel gene encoding a putative transmembrane protein is mutated in gnathodiaphyseal dysplasia (GDD).
abstract: Gnathodiaphyseal dysplasia (GDD) is a rare skeletal syndrome characterized by bone fragility, sclerosis of tubular bones, and cemento-osseous lesions of the jawbone. By linkage analysis of a large Japanese family with GDD, we previously mapped the GDD locus to chromosome 11p14.3-15.1. In the critical region determined by recombination mapping, we identified a novel gene (GDD1) that encodes a 913-amino-acid protein containing eight putative transmembrane-spanning domains. Two missense mutations (C356R and C356G) of GDD1 were identified in the two families with GDD (the original Japanese family and a new African American family), and both missense mutations occur at the cysteine residue at amino acid 356, which is evolutionarily conserved among human, mouse, zebrafish, fruit fly, and mosquito. Cellular localization to the endoplasmic reticulum suggests a role for GDD1 in the regulation of intracellular calcium homeostasis.
authors.affiliation: First Department of Oral and Maxillofacial Surgery, University of Tokushima, Tokushima, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Tsutsumi
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Kamata
authors.forename: Tamara J
authors.initials: TJ
authors.lastname: Vokes
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Maruoka
authors.forename: Koichi
authors.initials: K
authors.lastname: Nakakuki
authors.forename: Shoji
authors.initials: S
authors.lastname: Enomoto
authors.forename: Ken
authors.initials: K
authors.lastname: Omura
authors.forename: Teruo
authors.initials: T
authors.lastname: Amagasa
authors.forename: Masaru
authors.initials: M
authors.lastname: Nagayama
authors.forename: Fumiko
authors.initials: F
authors.lastname: Saito-Ohara
authors.forename: Johji
authors.initials: J
authors.lastname: Inazawa
authors.forename: Maki
authors.initials: M
authors.lastname: Moritani
authors.forename: Takashi
authors.initials: T
authors.lastname: Yamaoka
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Inoue
authors.forename: Mitsuo
authors.initials: M
authors.lastname: Itakura
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D016466:CHO Cells; D002118:Calcium / Q000378:metabolism; D003966:Camurati-Engelmann Syndrome / Q000235:genetics*; D002874:Chromosome Mapping; D002880:Chromosomes, Human, Pair 11; D003001:Cloning, Molecular; D006224:Cricetinae; D004721:Endoplasmic Reticulum / Q000378:metabolism; D005260:Female; D005799:Genes, Dominant; D008040:Genetic Linkage; D006801:Humans; D007569:Jaw Abnormalities / Q000235:genetics*; D008126:Lod Score; D008297:Male; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D020125:Mutation, Missense / Q000235:genetics*; D010375:Pedigree; D017386:Sequence Homology, Amino Acid; D014018:Tissue Distribution; D014162:Transfection
chemical_list: D008565:Membrane Proteins; D002118:Calcium