title: Identification of a new mutation in an Iranian family with hereditary multiple osteochondromas.
abstract: BACKGROUND
  Hereditary multiple osteochondromas (HMO), previously named hereditary multiple exostoses (HME), is an autosomal dominant skeletal disorder characterized by the growth of multiple osteochondromas and is associated with bony deformity, skeletal growth reduction, nerve compression, restriction of joint motion, and premature osteoarthrosis. HMO is genetically heterogeneous, localized on at least three chromosomal loci including 8q24.1 (EXT1), 11p11-p13 (EXT2), and 19p (EXT3). The median age of diagnosis is 3 years; almost all affected individuals are diagnosed by age 12. The risk for malignant degeneration to osteochondrosarcoma increases with age, although the lifetime risk of malignant degeneration is low (~1%).
  
  
  RESULTS
  This study was performed on an Iranian family with nine affected individuals from three consecutive generations. Here, the proband was an affected woman who received genetic counseling prior to pregnancy. All exons of the three genes were examined in the proband using polymerase chain reaction and sequencing methods (the last member of this family is a male with severe deformities and lesions, especially around his large joints). Exon 4 ofEXT1(c.1235 G>A) was changed in affected individuals. This mutation alters tryptophan to a premature stop codon on amino acid position 412 (p.Trp412x).
  
  
  CONCLUSIONS
  The outcome of this study has extended the genotypic spectrum of Iranian patients with HMO, revealing a way for improving detection and genetic counseling in carriers.
authors.affiliation: Mofid Children's Hospital, Shahid Beheshti University of Medical Sciences.
authors.forename: Susan
authors.initials: S
authors.lastname: Akbaroghli
authors.affiliation: ENT and Head & Neck Research Center and Department, Iran University of Medical Sciences (IUMS).
authors.forename: Maryam
authors.initials: M
authors.lastname: Balali
authors.affiliation: Medical Genetics Department, School of Medicine, Shahid Beheshti University of Medical Sciences; Medical Genetics Department, National Institute for Genetic Engineering and Biotechnology.
authors.forename: Behnam
authors.initials: B
authors.lastname: Kamalidehghan
authors.affiliation: Medical Genetics Department, National Institute for Genetic Engineering and Biotechnology.
authors.forename: Siamak
authors.initials: S
authors.lastname: Saber
authors.affiliation: Department of Neuroscience, Iran Medical University, Tehran, Iran.
authors.forename: Omid
authors.initials: O
authors.lastname: Aryani
authors.affiliation: Department of Veterinary Preclinical Sciences, Faculty of Veterinary Medicine, Universiti Putra Malaysia (UPM), Serdang, Malaysia.
authors.forename: Goh Yong
authors.initials: GY
authors.lastname: Meng
authors.affiliation: Medical Genetics Department, National Institute for Genetic Engineering and Biotechnology.
authors.forename: Massoud
authors.initials: M
authors.lastname: Houshmand
keywords: EXT1 and EXT2; HME; HMO; bony exostoses; c.1235 G>A; exon 4 of EXT1; hereditary multiple exostoses