title: The diagnostic utility of the GNAS mutation in patients with fibrous dysplasia: meta-analysis of 168 sporadic cases.
abstract: GNAS mutations have been implicated in the development of fibrous dysplasia and multiple endocrinopathies of the Albright-McCune syndrome. To investigate the diagnostic utility of GNAS mutations in patients with fibrous dysplasia, we performed mutational analyses of histologically confirmed fibrous dysplasia and conducted a meta-analysis of the literature. We collected 48 cases of fibrous dysplasia from 3 institutions from 2002 to 2011 and performed polymerase chain reaction and direct bidirectional sequencing of exons 8 and 9 of GNAS using paraffin-embedded tissues. We searched MEDLINE, PubMed, and the KoreaMed databases from 1997 to 2011 and included an additional 155 cases of fibrous dysplasia from 8 representative studies to conduct a meta-analysis. In our sample, 28 (58.3%) of 48 cases showed point mutations of codon 201 at exon 8. Twenty-five cases had a substitution of arginine at codon 201 for histidine (p.R201H), and 3 cases had a substitution for cysteine (p.R201C). One case had a new mutation at codon 224 (p.V224A). The incidence of GNAS mutations was significantly greater in cases that involved long bones than in cases that involved flat bones (P = .017) and was higher in polyostotic cases than in monostotic cases (P = .067). In meta-analysis, 9 studies and 203 patients were included. The overall positive rate of GNAS mutation in fibrous dysplasia was 71.9% (146/203). The major types of mutations were missense mutations such as R201H (66.4%) and R201C (30.8%). As a result, the detection of GNAS mutation could be a valuable adjunct to conventional histopathologic diagnosis of fibrous dysplasia.
authors.affiliation: Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, 135-710 South Korea.
authors.forename: Seung Eun
authors.initials: SE
authors.lastname: Lee
authors.forename: Eun Hee
authors.initials: EH
authors.lastname: Lee
authors.forename: Heejung
authors.initials: H
authors.lastname: Park
authors.forename: Ji-Youn
authors.initials: JY
authors.lastname: Sung
authors.forename: Hyoun Wook
authors.initials: HW
authors.lastname: Lee
authors.forename: So Young
authors.initials: SY
authors.lastname: Kang
authors.forename: Sungwook
authors.initials: S
authors.lastname: Seo
authors.forename: Byung Heon
authors.initials: BH
authors.lastname: Kim
authors.forename: Hyojin
authors.initials: H
authors.lastname: Lee
authors.forename: An Na
authors.initials: AN
authors.lastname: Seo
authors.forename: Geunghwan
authors.initials: G
authors.lastname: Ahn
authors.forename: Yoon-La
authors.initials: YL
authors.lastname: Choi
mesh_terms: D000293:Adolescent; D000328:Adult; D001842:Bone and Bones / Q000473:pathology*; D002648:Child; D002675:Child, Preschool; D002864:Chromogranins; D004252:DNA Mutational Analysis; D005260:Female; D005357:Fibrous Dysplasia of Bone / Q000175:diagnosis* / Q000235:genetics; D019205:GTP-Binding Protein alpha Subunits, Gs / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense
chemical_list: D002864:Chromogranins; C406732:GNAS protein, human; D019205:GTP-Binding Protein alpha Subunits, Gs