Early onset Paget's disease of bone caused by a novel mutation (78dup27) of the TNFRSF11A gene in a Chinese family
Early onset Paget's disease of bone caused by a novel mutation (78dup27) of the TNFRSF11A gene in a Chinese family
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DOI：
10.1038/aps.2009.90
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发表时间：
2009-08-01
影响因子：
8.2
通讯作者：
Zhang, Zhen-lin
中科院分区：
文献类型：
--
作者：
Ke, Yao-hua;Yue, Hua;Zhang, Zhen-lin
目的：先前的一项研究表明，早发性家族性佩吉特骨病（PDB）的日本血统个体在编码RANK的TNFRSF 11 A基因的第75位（75 dup 27）携带27 bp重复。本文报道了一个早发性PDB家系中TNFRSF 11 A基因第1外显子78 dup 27突变的发现。方法：对一个早发性PDB家系进行临床和遗传学研究。结果：在4例患者和1例无症状患者中发现TNFRSF 11 A基因第1外显子（78 dup 27）的一个新的27-bp重复序列。尽管这种重复与先前鉴定的突变长度相同（27 bp，从碱基78到104），但在我们的患者中，RANK信号肽中的9个重复氨基酸是LLLLCALLA。在这个家庭中的受影响的个人的表型重叠早发PDB和经典PDB，但在我们的患者中发现了几个显着的特点。我们的家族性PDB和日本早发性PDB之间的关键区别在于发病年龄，在我们的大多数患者中，发病年龄在20多岁（先证者的侄女除外）。另一个显着的差异是，先证者的儿子（24岁），谁携带78 dup 27突变，没有临床症状或骨异常，除了增加血清ALP，OC和CTX.Conclusion：我们的研究结果可能会提供一个更好的了解早发性PDB的临床特征，并支持TNFRSF 11 A基因外显子1突变热点的概念。
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 1 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 1 of the TNFRSF11A gene.