J Korean Soc Endocrinol.  2005 Apr;20(2):142-147.

Mutational Analysis of Gsalpha Protein in Fibrous dysplasia of the Bone

• Rhee SY
• Woo JT
• Koh G
• Oh S
• Kim SW
• Kim JW
• Kim YS
• Park YK

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 Gsalpha protein, which is responsible for intracellular signal transduction.
METHODS
Mutations in the GNAS1 gene, which codes for Gsalpha 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

MeSH Terms

Bone and Bones
Clone Cells
Cloning, Organism
Congenital Abnormalities
DNA
Exons
Extremities
Fibrous Dysplasia, Polyostotic
Fractures, Spontaneous
GTP-Binding Protein alpha Subunits
Humans
Introns
Paraffin
Plasmids
Point Mutation
Polymerase Chain Reaction
Sequence Analysis, DNA
Signal Transduction
DNA
GTP-Binding Protein alpha Subunits
Paraffin

Figure

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  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.

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