Abstract
Familial florid osseous dysplasia (FFOD) is an autosomal dominant disorder of connective tissue, characterized by lobulated cementum-like masses scattered throughout the jaws and the alveolar process. This study aimed to identify the genetic etiology of a three-generation Chinese family affected with FFOD. A novel missense mutation p.C356W in anoctamin 5 (ANO5) gene was successfully identified as the pathogenic mutation by whole-exome sequencing (WES). The p.C356W mutation is located in the first loop between the first and second transmembrane domain of ANO5 protein. Sequence alignment of ANO5 protein among many different species revealed that this position is highly conserved. The p.C356W mutation may damage the predicted protein stability of ANO5 by altering the structure of several extracellular loops of ANO5 and affecting the formation of the disulfide bond, thereby disrupting the correct folding of ANO5 protein. Thus, the amino acid at position 356 appears to play a key role in the protein structural stability and function of ANO5 protein. Our results may also provide new insights into the cause and diagnosis of FFOD and may have implications for genetic counseling and clinical management.
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Acknowledgements
This research was supported by The National Key Research and Development Program of China (2016YFC0902700), Shanghai Municipal Commission of Health and Family Planning (20174Y0025), Training Program for Clinical Medical Young Talents of Shanghai (to Guoling You), Chen Xing Excellent Young Teacher Training Program of Shanghai Jiao Tong University (to Guoling You), and the National Natural Science Foundation of China (81601847). We thank the patients and family members for their participation in this study.
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ML and GY performed the experiments; ML, GY, JL, and Jinbing Wang analyzed the data; GY, AG, and ML wrote and polished the paper; QF, JL, and JS conceived and supervised the experiments.
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Lv, M., You, G., Wang, J. et al. Identification of a novel ANO5 missense mutation in a Chinese family with familial florid osseous dysplasia. J Hum Genet 64, 599–607 (2019). https://doi.org/10.1038/s10038-019-0601-9
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DOI: https://doi.org/10.1038/s10038-019-0601-9
