Early onset Paget＇s disease of bone caused by a novel mutation （78dup27） of the TNFRSF11A gene in a Chinese family  

作　　者：Yao-hua KE Hua YUE Jin-wei HE Yu-juan LIU Zhen-lin ZHANG 

机构地区：[1]The Department of Osteoporosis, Metabolic Bone Disease and Genetic Research Unit, Shanghai Jiao Tong University Affiliated SixthPeople's Hospital, Shanghai 200233, China

出　　处：《Acta Pharmacologica Sinica》2009年第8期1204-1210,共7页中国药理学报（英文版）

基　　金：Acknowledgements This project was supported by the National Natural Science Foundation of China （No 30570891, 30771019, and 30800387） and the Program of Shanghai Subject Chief Scientist （No08XD1403000）, We thank the patients for their participation.

摘　　要：Aim： A previous study showed that individuals of Japanese descent affected by early onset familial Paget＇s disease of bone （PDB） carried a 27-bp duplication at position 75 （75dup27） in the TNFRSF11A gene encoding RANK. Here we report the identification of a novel mutation （78dup27） in exon I of TNFRSF11A in a Chinese family with early onset PDB. Methods： We conducted clinical and genetic studies in a non-consanguineous Chinese family with early onset PDB. The entire coding region of TNFRSF11A was amplified and directly sequenced directly. Results： A novel 27-bp duplication in exon 1 （78dup27） in TNFRSF11A was found in four affected individuals and one asymptomatic individual. Although this duplication was the same length as the previously identified mutation （27 bp, from bases 78 to 104）, in our patients the nine duplicated amino acids in the RANK signal peptide were LLLLCALLA. The phenotypes of affected individuals in this family overlapped with both early onset PDB and classic PDB, but several distinguishing features were found in our patients. The key difference between our familial PDB and the Japanese early onset PDB was the age of onset, which in most of our patients was during their late 20s （except for the propositus＇ niece）. Another notable difference was that the propositus＇ son （24 years old）, who carried the 78dup27 mutation, had no clinical symptoms or bone abnormalities, except for increased serum ALP, OC and CTX. Conclusion： Our findings may provide a better understanding of the clinical features of early onset PDB and support the notion of a hot spot for mutations in exon I of the TNFRSF11A gene.Aim： A previous study showed that individuals of Japanese descent affected by early onset familial Paget＇s disease of bone （PDB） carried a 27-bp duplication at position 75 （75dup27） in the TNFRSF11A gene encoding RANK. Here we report the identification of a novel mutation （78dup27） in exon I of TNFRSF11A in a Chinese family with early onset PDB. Methods： We conducted clinical and genetic studies in a non-consanguineous Chinese family with early onset PDB. The entire coding region of TNFRSF11A was amplified and directly sequenced directly. Results： A novel 27-bp duplication in exon 1 （78dup27） in TNFRSF11A was found in four affected individuals and one asymptomatic individual. Although this duplication was the same length as the previously identified mutation （27 bp, from bases 78 to 104）, in our patients the nine duplicated amino acids in the RANK signal peptide were LLLLCALLA. The phenotypes of affected individuals in this family overlapped with both early onset PDB and classic PDB, but several distinguishing features were found in our patients. The key difference between our familial PDB and the Japanese early onset PDB was the age of onset, which in most of our patients was during their late 20s （except for the propositus＇ niece）. Another notable difference was that the propositus＇ son （24 years old）, who carried the 78dup27 mutation, had no clinical symptoms or bone abnormalities, except for increased serum ALP, OC and CTX. Conclusion： Our findings may provide a better understanding of the clinical features of early onset PDB and support the notion of a hot spot for mutations in exon I of the TNFRSF11A gene.

关 键 词：Paget＇s disease of bone RANK MUTATION 

分 类 号：Q78[生物学—分子生物学] C913.1[经济管理]