title: Large-scale mutational analysis in the EXT1 and EXT2 genes for Japanese patients with multiple osteochondromas.
abstract: BACKGROUND
  Multiple osteochondroma (MO) is an autosomal dominant skeletal disorder characterized by the formation of multiple osteochondromas, and exostosin-1 (EXT1) and exostosin-2 (EXT2) are major causative genes in MO. In this study, we evaluated the genetic backgrounds and mutational patterns in Japanese families with MO.
  
  
  RESULTS
  We evaluated 112 patients in 71 families with MO. Genomic DNA was isolated from peripheral blood leucocytes. The exons and exon/intron junctions of EXT1 and EXT2 were directly sequenced after PCR amplification. Fifty-two mutations in 47 families with MO in either EXT1 or EXT2, and 42.3% (22/52) of mutations were novel mutations. Twenty-nine families (40.8%) had mutations in EXT1, and 15 families (21.1%) had mutations in EXT2. Interestingly, three families (4.2%) had mutations in both EXT1 and EXT2. Twenty-four families (33.8%) did not exhibit mutations in either EXT1 or EXT2. With regard to the types of mutations identified, 59.6% of mutations were inactivating mutations, and 38.5% of mutations were missense mutations.
  
  
  CONCLUSIONS
  We found that the prevalence of EXT1 mutations was greater than that of EXT2 mutations in Japanese MO families. Additionally, we identified 22 novel EXT1 and EXT2 mutations in this Japanese MO cohort. This study represents the variety of genotype in MO.
authors.affiliation: Department of Orthopaedic Surgery, Gifu University, Graduate School of Medicine, 1-1, Yanagido, Gifu, 501-1194, Japan. ishidaiishidai@kha.biglobe.ne.jp.
authors.forename: Daichi
authors.initials: D
authors.lastname: Ishimaru
authors.affiliation: Research Center for Medical Glycoscience (RCMG), National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba, Japan. masa-gotoh@aist.go.jp.
authors.forename: Masanori
authors.initials: M
authors.lastname: Gotoh
authors.affiliation: Department of Orthopedic Surgery, National Research Institute for Child Health and Development, Tokyo, Japan. takayama-s@ncchd.go.jp.
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Takayama
authors.affiliation: Division of Medical Genetics, National Center for Child Health and Development, Tokyo, Japan. kosaki-r@ncchd.go.jp.
authors.forename: Rika
authors.initials: R
authors.lastname: Kosaki
authors.affiliation: Department of Orthopaedic Surgery, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. ymatsu@ortho.med.kyushu-u.ac.jp.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Matsumoto
authors.affiliation: Research Center for Medical Glycoscience (RCMG), National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba, Japan. h.narimatsu@aist.go.jp.
authors.forename: Hisashi
authors.initials: H
authors.lastname: Narimatsu
authors.affiliation: Research Center for Medical Glycoscience (RCMG), National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba, Japan. takashi-sato@aist.go.jp.
authors.forename: Takashi
authors.initials: T
authors.lastname: Sato
authors.affiliation: Advanced Medical Research Center, Aichi Medical University, Nagakute, Aichi, Japan. kimata@aichi-med-u.ac.jp.
authors.forename: Koji
authors.initials: K
authors.lastname: Kimata
authors.affiliation: Department of Orthopaedic Surgery, Gifu University, Graduate School of Medicine, 1-1, Yanagido, Gifu, 501-1194, Japan. hakiyama@gifu-u.ac.jp.
authors.forename: Haruhiko
authors.initials: H
authors.lastname: Akiyama
authors.affiliation: Spine Center, Gifu Municipal Hospital, Gifu, Japan. katsuji.spine@gmail.com.
authors.forename: Katsuji
authors.initials: K
authors.lastname: Shimizu
authors.affiliation: Department of Orthopaedic Surgery, Gifu University, Graduate School of Medicine, 1-1, Yanagido, Gifu, 501-1194, Japan. mkazuu@gifu-u.ac.jp.
authors.forename: Kazu
authors.initials: K
authors.lastname: Matsumoto
mesh_terms: D044466:Asian People / Q000235:genetics*; D004252:DNA Mutational Analysis; D005091:Exons; D005097:Exostoses, Multiple Hereditary / Q000175:diagnosis* / Q000235:genetics*; D005260:Female; D005820:Genetic Testing; D006801:Humans; D007438:Introns; D008297:Male; D020125:Mutation, Missense; D017351:N-Acetylglucosaminyltransferases / Q000235:genetics*; D000099065:Exostosin 2; D000099058:Exostosin 1
chemical_list: D017351:N-Acetylglucosaminyltransferases; D000099058:Exostosin 1; D000099065:Exostosin 2