Binghui Zeng1,2,3, Junkun Liao1,2, Hanqing Zhang1,2, Sha Fu4, Weixiong Chen1,2, Guokai Pan1,2, Qunxing Li1,2, Weiliang Chen1,2, Soldano Ferrone5, Binghao Wu6, Sheng Sun7, Jiali Hu8, Michael Ho-Young Ahn5, Zhaoyu Lin1,2, Dongsheng Yu3, Zhanpeng Ou1,2, Xinhui Wang5, Fengbo Mo5, Nasi Huang5,9, James A Hamilton9, Jinsong Li1,2, Song Fan1,2,5. 1. Department of Oral and Maxillofacial Surgery, Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University, Guangzhou, China. 2. Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation of Sun Yat-Sen Memorial Hospital, Guangzhou, China. 3. Guanghua School of Stomatology, Hospital of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-sen University, Guangzhou, China. 4. Department of Pathology, Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University, Guangzhou, China. 5. Division of Surgical Oncology, Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts. 6. Key Laboratory of Systems Biomedicine (Ministry of Education) and Collaborative Innovation Center of Systems Biomedicine of Rui-Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. 7. Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, Massachusetts. 8. State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China. 9. Physiology and Biophysics, Boston University, Boston, Massachusetts.
Abstract
BACKGROUND: Gnathodiaphyseal dysplasia (GDD) is a rare skeletal disorder that has not been well studied. METHODS: Sanger sequencing, whole-genome sequencing (WGS), and bioinformatics and structural modeling analyses were performed. RESULTS: A family with patients with fibro-osseous lesions of the jawbones were initially diagnosed with cherubism. Sequencing of SH3BP2, which is the causal gene of cherubism, revealed no pathogenic mutation. Through WGS, we identified a novel mutation c.1067G>T (p.C356F) in ANO5, and bioinformatics analyses and structural modeling showed that the mutation was deleterious. Because ANO5 is the gene responsible for GDD, we reappraised the clinical data of the patients, and the diagnosis was corrected to atypical GDD. A review of the literature showed that 67% of GDD cases confirmed by molecular testing were initially misdiagnosed. CONCLUSIONS: The novel mutation c.1067G>T (p.C356F) in ANO5 is responsible for the atypical GDD observed in our patients. GDD should be included in the differential diagnosis for patients with fibro-osseous lesions.
BACKGROUND: Gnathodiaphyseal dysplasia (GDD) is a rare skeletal disorder that has not been well studied. METHODS: Sanger sequencing, whole-genome sequencing (WGS), and bioinformatics and structural modeling analyses were performed. RESULTS: A family with patients with fibro-osseous lesions of the jawbones were initially diagnosed with cherubism. Sequencing of SH3BP2, which is the causal gene of cherubism, revealed no pathogenic mutation. Through WGS, we identified a novel mutation c.1067G>T (p.C356F) in ANO5, and bioinformatics analyses and structural modeling showed that the mutation was deleterious. Because ANO5 is the gene responsible for GDD, we reappraised the clinical data of the patients, and the diagnosis was corrected to atypical GDD. A review of the literature showed that 67% of GDD cases confirmed by molecular testing were initially misdiagnosed. CONCLUSIONS: The novel mutation c.1067G>T (p.C356F) in ANO5 is responsible for the atypical GDD observed in our patients. GDD should be included in the differential diagnosis for patients with fibro-osseous lesions.
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