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Rhee, Woo, Koh, Oh, Kim, Kim, Kim, and Park: Mutational Analysis of Gsα Protein in Fibrous dysplasia of the Bone
Original Article
Journal of Korean Society of Endocrinology

Journal of Korean Society of Endocrinology 2005; 20(2): 142-147.

Published online: 20 April 2005

DOI: https://doi.org/10.3803/jkes.2005.20.2.142

Mutational Analysis of Gsα Protein in Fibrous dysplasia of the Bone

Sang Youl Rhee1, Jeong-taek Woo1, 2, Gwanpyo Koh1, 2, Seungjoon Oh1, 2, Sung Woon Kim1, Jin-Woo Kim1, 2, Young Seol Kim1, Yong-Koo Park3

1Department of Endocrinology and Metabolism, School of Medicine, Kyung Hee University, Seoul, Korea.

2Research Institute of Endocrinology, School of Medicine, Kyung Hee University, Seoul, Korea.

3Department of Pathology, School of Medicine, Kyung Hee University, Seoul, Korea.

Received 17 November 2004       Accepted 21 March 2005

Copyright © 2005 Korean Endocrine Society

Abstract

Background

Fibrous dysplasia of the bone (FD) is a benign fibrous bone lesion which usually involves the long bones of the extremities. FD may be asymptomatic, but often leads to bone deformity and pathological fracture. The disease is caused by a somatic mutation in the Gsα protein, which is responsible for intracellular signal transduction.

Methods

Mutations in the GNAS1 gene, which codes for Gsα protein, was investigated in 34 patients with monostotic and polyostotic FD and McCune-Albright syndrome. DNA was extracted from formalin-fixed, paraffin embedded bone tissues, and exons 8 and 9 of the GNAS1 gene amplified using a polymerase chain reaction (PCR). Subsequently, plasmid cloning and DNA sequencing analysis were performed.

Results

The PCR was successfully performed in 5 patients with monostotic FD. However, the sequencing analysis failed to identify any significant point mutations in exons 8 or 9 of GNAS1. Nevertheless, 3 point mutations were observed in the intron of the GNAS1 gene in 2 samples.

Conclusion

In addition to the previously known somatic mutations of the GNAS1 gene, this study suggests that fibrous dysplasia of the bone might be associated with another point mutations of the GNAS1 gene.

Keywords: Fibrous dysplasia, McCune-Albright syndrome, GNAS1, GTP-Binding Protein alpha Subunits, Gs

Figures and Tables

Fig. 1
Analyses of gene mutations in patients with fibrous dysplasia. The figures show the intron sequences of the GNAS1 gene. Point mutations (arrowed) were observed in the introns of the 27th and 33rd samples, and these were amplified by using a primer for exon 8. Another point mutation was observed in an intron of the 27th sample, and this was amplified by using a primer for exon 9.
jkse-20-142-g001
Table 1
Oligonucleotide Primers Used for PCR Amplification of Exon 8 and Exon 9 in the GNAS1 Gene
jkse-20-142-i001
Table 2
Sites of Involved Bone in Patients with Fibrous Dysplasia
jkse-20-142-i002

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