title: Two novel compound heterozygous BMP1 mutations in a patient with osteogenesis imperfecta: a case report.
abstract: BACKGROUND
  Osteogenesis imperfecta (OI) is a collagen-related bone dysplasia leading to a susceptibility to fractures. OI can be caused by mutations in several genes including BMP1. It encodes two isoforms, bone morphogenetic protein 1 (BMP1) and mammalian tolloid (mTLD); both have proteolytic activity to remove the C-propeptide from procollagen.
  
  
  METHODS
  We report a Thai OI patient who had his first fracture at the age of three months. Using next generation sequencing, we successfully identified two novel compound heterozygous BMP1 mutations. One mutation, c.796_797delTT (p.Phe266Argfs*25) affects both BMP1 and mTLD isoforms, while the other, c.2108-2A > G, affects only the BMP1 isoform. Preservation of the mTLD may explain the relatively less severe clinical phenotype in this patient. Intravenous bisphosphonate was given from the age of 8 months to 5 years. He was free from fractures for 9 months before discontinuation.
  
  
  CONCLUSIONS
  This case expands the mutation spectrum of BMP1, strengthens the correlation between genotype and phenotype, and supports the benefits of bisphosphonate in OI patients with BMP1 mutations.
authors.affiliation: Department of Orthopaedics, Faculty of Medicine, Chiang Mai University, Chiang Mai, 50200, Thailand.|Center of Excellence for Medical Genetics, Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, Bangkok, 10330, Thailand.|Excellence Center for Medical Genetics, King Chulalongkorn Memorial Hospital, The Thai Red Cross Society, Bangkok, 10330, Thailand.
authors.forename: Apiruk
authors.initials: A
authors.lastname: Sangsin
authors.affiliation: Department of Pediatrics, Queen Sirikit National Institute of Child Health, Bangkok, 10400, Thailand.
authors.forename: Chulaluck
authors.initials: C
authors.lastname: Kuptanon
authors.affiliation: Center of Excellence for Medical Genetics, Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, Bangkok, 10330, Thailand.|Excellence Center for Medical Genetics, King Chulalongkorn Memorial Hospital, The Thai Red Cross Society, Bangkok, 10330, Thailand.
authors.forename: Chalurmpon
authors.initials: C
authors.lastname: Srichomthong
authors.affiliation: Department of Mathematics and Computer Science, Faculty of Science, Chulalongkorn University, Bangkok, 10330, Thailand.|Program in Bioinformatics and Computational Biology, Graduate School, Chulalongkorn University, Bangkok, 10330, Thailand.
authors.forename: Monnat
authors.initials: M
authors.lastname: Pongpanich
authors.affiliation: Center of Excellence for Medical Genetics, Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, Bangkok, 10330, Thailand. kanya.su@chula.ac.th.|Excellence Center for Medical Genetics, King Chulalongkorn Memorial Hospital, The Thai Red Cross Society, Bangkok, 10330, Thailand. kanya.su@chula.ac.th.|Division of Medical Genetics and Metabolism, Department of Pediatrics, King Chulalongkorn Memorial Hospital, Sor Kor Building 11th floor, Bangkok, 10330, Thailand. kanya.su@chula.ac.th.
authors.forename: Kanya
authors.initials: K
authors.lastname: Suphapeetiporn
authors.affiliation: Center of Excellence for Medical Genetics, Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, Bangkok, 10330, Thailand.|Excellence Center for Medical Genetics, King Chulalongkorn Memorial Hospital, The Thai Red Cross Society, Bangkok, 10330, Thailand.
authors.forename: Vorasuk
authors.initials: V
authors.lastname: Shotelersuk
mesh_terms: D015519:Bone Density; D055395:Bone Morphogenetic Protein 1 / Q000235:genetics*; D002648:Child; D005269:Femur / Q000000981:diagnostic imaging; D017353:Gene Deletion; D005838:Genotype; D006579:Heterozygote; D006801:Humans; D008297:Male; D010013:Osteogenesis Imperfecta / Q000175:diagnosis / Q000235:genetics*; D020033:Protein Isoforms / Q000235:genetics
chemical_list: D020033:Protein Isoforms; D055395:Bone Morphogenetic Protein 1
keywords: BMP1; Case report; Mutation analysis; Next generation sequencing; Osteogenesis imperfecta