Genotype and phenotype analysis of Taiwanese patients with osteogenesis imperfecta

Hsiang-Yu Lin¹²³⁴⁵, Chih-Kuang Chuang³⁶⁷, Yi-Ning Su⁸, Ming-Ren Chen¹²⁴, Hui-Chin Chiu², Dau-Ming Niu⁵⁹ and Shuan-Pei Lin¹¹⁰²³⁴^*

*Corresponding author: Shuan-Pei Lin zsplin14@gmail.com

Author Affiliations

¹Department of Medicine, Mackay Medical College, New Taipei City, Taiwan

²Department of Pediatrics, Mackay Memorial Hospital, No. 92, Sec. 2, Chung-Shan North Road, Taipei 10449, Taiwan

³Department of Medical Research, Mackay Memorial Hospital, Taipei, Taiwan

⁴Mackay Medicine, Nursing and Management College, Taipei, Taiwan

⁵Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan

⁶Medical College, Fu-Jen Catholic University, Taipei, Taiwan

⁷Institute of Biotechnology, National Taipei University of Technology, Taipei, Taiwan

⁸Department of Obstetrics and Gynecology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan

⁹Department of Pediatrics, Taipei Veterans General Hospital, Taipei, Taiwan

¹⁰Department of Infant and Child Care, National Taipei University of Nursing and Health Sciences, Taipei, Taiwan

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Orphanet Journal of Rare Diseases 2015, 10:152 doi:10.1186/s13023-015-0370-2

The electronic version of this article is the complete one and can be found online at:http://www.ojrd.com/content/10/1/152

Received:	28 August 2015
Accepted:	22 November 2015
Published:	1 December 2015

Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

Abstract

Background

Osteogenesis imperfecta (OI) is a congenital disorder characterized by increased bone fragility and low bone mass.

Methods

The presence of COL1A1 or COL1A2 mutation was investigated by direct sequencing in 72 patients with OI type I, III, or IV (27 males and 45 females; age range 0.2-62 years) from 37 unrelated families. The clinical features of these patients were also recorded.

Results

Thirty-seven COL1A1 and COL1A2 mutations were identified, including 28 COL1A1 mutations and 9COL1A2 mutations. Fifteen (41 %) were novel mutations, and twelve (32 %) were familial mutations. A review of their medical records revealed that the 72 patients could be classified into OI type I (n = 42), III (n = 5), and IV (n = 25). Twenty-nine patients had helical mutations (caused by the substitution of a glycine within the Gly-X-Y triplet domain of the triple helix), and 42 had haploinsufficiency mutations (caused by frameshift, nonsense, and splice-site mutations). Compared with haploinsufficiency, the patients with helical mutations had more severely impaired skeletal phenotypes, including shorter height, lower bone mineral density, poorer walking ability, more frequent manifestations of dentinogenesis imperfecta and scoliosis (p < 0.05).