title: Autosomal dominant gnathodiaphyseal dysplasia maps to chromosome 11p14.3-15.1.
abstract: Gnathodiaphyseal dysplasia (GDD) is a syndrome characterized by bone fragility, sclerosis of tubular bones, and cemento-osseous lesions of jawbones. Although some cases of this syndrome exist in families with autosomal dominant inheritance, the underlying gene has never been identified. We analyzed a large four-generation family with GDD by linkage analysis using genomic DNA from nine affected and six nonaffected family members. A genome-wide search using a set of highly polymorphic microsatellite markers showed evidence for linkage to chromosome 11p14.3-15.1. Two-point linkage analysis of microsatellite markers spanning this locus resulted in a maximum logarithm of odds (LOD) score of 2.70 with a recombination fraction (theta) of 0 at D11S1755, D11S1759, and D11S915, and a maximum LOD score of 3.01 at D11S4114 was obtained in multipoint linkage analysis. Haplotype analysis detected no recombination between GDD and six closely linked markers (D11S928, D11S1755, D11S4114, D11S1759, D11S915, and D11S929) and established the candidate interval of 8.7 cM on chromosome 11p for GDD. Although GDD has been considered to be a variation of osteogenesis imperfecta (MIM 166260), our results indicate that this syndrome is a new and distinct disease entity from other systemic bone diseases. Furthermore, these genetic markers are useful for presymptomatic diagnosis of GDD in some families and for identification of the GDD gene.
authors.affiliation: First Department of Oral and Maxillofacial Surgery, School of Dentistry, The 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: Yutaka
authors.initials: Y
authors.lastname: Maruoka
authors.forename: Miki
authors.initials: M
authors.lastname: Ando
authors.forename: Osamu
authors.initials: O
authors.lastname: Tezuka
authors.forename: Shoji
authors.initials: S
authors.lastname: Enomoto
authors.forename: Ken
authors.initials: K
authors.lastname: Omura
authors.forename: Masaru
authors.initials: M
authors.lastname: Nagayama
authors.forename: Eiji
authors.initials: E
authors.lastname: Kudo
authors.forename: Maki
authors.initials: M
authors.lastname: Moritani
authors.forename: Takashi
authors.initials: T
authors.lastname: Yamaoka
authors.forename: Mitsuo
authors.initials: M
authors.lastname: Itakura
mesh_terms: D001847:Bone Diseases / Q000235:genetics*; D002874:Chromosome Mapping; D002880:Chromosomes, Human, Pair 11; D005260:Female; D005799:Genes, Dominant; D008040:Genetic Linkage; D006801:Humans; D007571:Jaw Diseases / Q000235:genetics*; D008126:Lod Score; D008297:Male; D010375:Pedigree