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Identification of a new mutation in an Iranian family with hereditary multiple osteochondromas

Authors Akbaroghli S, Balali M, Kamalidehghan B, Saber S, Aryani O, Yong Meng G, Houshmand M

Received 30 April 2016

Accepted for publication 15 October 2016

Published 20 December 2016 Volume 2017:13 Pages 15—19


Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 3

Editor who approved publication: Professor Garry Walsh

Susan Akbaroghli,1,* Maryam Balali,2,* Behnam Kamalidehghan,3,4 Siamak Saber,4 Omid Aryani,5 Goh Yong Meng,6 Massoud Houshmand4

1Mofid Children’s Hospital, Shahid Beheshti University of Medical Sciences, 2ENT and Head & Neck Research Center and Department, Iran University of Medical Sciences (IUMS), 3Medical Genetics Department, School of Medicine, Shahid Beheshti University of Medical Sciences, 4Medical Genetics Department, National Institute for Genetic Engineering and Biotechnology, 5Department of Neuroscience, Iran Medical University, Tehran, Iran; 6Department of Veterinary Preclinical Sciences, Faculty of Veterinary Medicine, Universiti Putra Malaysia (UPM), Serdang, Malaysia

*These authors contributed equally to this work

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%).
Methods and 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 of EXT1 (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).
Conclusion: 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.

Keywords: bony exostoses, exon 4 of EXT1, HMO, hereditary multiple exostoses, HME, c.1235 G>A, EXT1 and EXT2

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