Seven novel and six de novo PHEX gene mutations in patients with hypophosphatemic rickets.
Seven novel and six de novo PHEX gene mutations in patients with hypophosphatemic rickets.
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低磷血症性佝偻病患者的 7 个新的 PHEX 基因突变和 6 个从头的 PHEX 基因突变
DOI：
10.3892/ijmm.2016.2796
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发表时间：
2016-12
影响因子：
5.4
通讯作者：
Zhang ZL
中科院分区：
文献类型：
--
作者：
Li SS;Gu JM;Yu WJ;He JW;Fu WZ;Zhang ZL
与X染色体上的内肽酶（PHEX）同源的磷酸盐调节基因的失活突变已被确定为X连锁低磷血症性佝偻病（XLH; OMIM 307800）的原因。在本研究中，我们招募了来自18个临床诊断为低磷血症性佝偻病的无血缘关系家庭的43名患者和250名健康对照。对于每个可用的个体，直接测序PHEX基因的所有22个外显子及其外显子-内含子边界。同时测定血清成纤维细胞生长因子23（FGF 23）水平。测序分析检测到17个不同的PHEX基因突变，其中7个被鉴定为新的：3个错义突变，包括c.304G>A（p.Gly102Arg）外显子3，c.229T>C（p.Cys77Arg）在外显子3和c.824T>C（p.Leu275Pro）外显子7; 2个缺失突变，包括c.528delT（p.Glu177LysfsX44）外显子5和c.1234delA（p.Ser412ValfsX12）; 2个选择性剪接突变，包括剪接供体位点内含子4的c.436_436+1delAG和剪接受体位点内含子13的c.1483-1G>C。此外，在6例散发病例中，6个突变被证明是新发的，且先证者均为女性。在250名健康对照中未发现突变。XLH患者血清FGF 23水平差异较大，与健康对照组比较无显著性差异。总的来说，这项研究的发现为PHEX突变谱提供了新的见解，并为PHEX蛋白中的关键结构域提供了潜在的证据。此外，发现XLH患者和健康对照之间的血清FGF 23水平的重叠表明其在XLH中的诊断价值有限。
Inactivating mutations in phosphate-regulating gene with homologies to endopeptidase on the X chromosome (PHEX) have been identified as a cause of X-linked hypophosphatemic rickets (XLH; OMIM 307800). In the present study, we enrolled 43 patients from 18 unrelated families clinically diagnosed with hypophosphatemic rickets and 250 healthy controls. For each available individual, all 22 exons with their exon-intron boundaries of the PHEX gene were directly sequenced. The levels of serum fibroblast growth factor 23 (FGF23) were measured as well. Sequencing analysis detected 17 different PHEX gene mutations, and 7 of these were identified as novel: 3 missense mutations, including c.304G>A (p.Gly102Arg) in exon 3, c.229T>C (p.Cys77Arg) in exon 3 and c.824T>C (p.Leu275Pro) in exon 7; 2 deletion mutations, including c.528delT (p.Glu177LysfsX44) in exon 5 and c.1234delA (p.Ser412ValfsX12) in exon 11; and 2 alternative splicing mutations, including c.436_436+1delAG in intron 4 at splicing donor sites and c.1483-1G>C in intron 13 at splicing acceptor sites. Moreover, 6 mutations were proven to be de novo in 6 sporadic cases and the probands were all females. No mutations were found in the 250 healthy controls. The serum levels of FGF23 varied widely among the patients with XLH, and no significant difference was found when compared with those of the healthy controls. On the whole, the findings of this study provide new insight into the spectrum of PHEX mutations and provide potential evidence of a critical domain in PHEX protein. In addition, the finding of an overlap of the serum FGF23 levels between the patients with XLH and the healthy controls indicates its limited diagnostic value in XLH.
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影响因子：
4.2
作者：
Jap, Tjin-Shing;Chiu, Chih-Yang;Niu, Dau-Ming;Levine, Michael A.
通讯作者：
Levine, Michael A.
影响因子：
4.4
作者：
Du, L;Desbarats, M;Ecarot, B
通讯作者：
Ecarot, B
影响因子：
5.8
作者：
Sabbagh, Y;Boileau, G;Tenenhouse, HS
通讯作者：
Tenenhouse, HS
DOI：
10.1016/j.bbrc.2012.06.042
发表时间：
2012-07-13
影响因子：
3.1
作者：
Kang, Qing-lin;Xu, Jia;Zhang, Zhen-lin
通讯作者：
Zhang, Zhen-lin
DOI：
10.1152/ajpendo.00008.2006
发表时间：
2006-07-01
影响因子：
5.1
作者：
Liu, Shiguang;Zhou, Jianping;Quarles, L. Darryl
通讯作者：
Quarles, L. Darryl