Three novel mutations in the PHEX gene in Chinese subjects with hypophosphatemic rickets extends genotypic variability.
Three novel mutations in the PHEX gene in Chinese subjects with hypophosphatemic rickets extends genotypic variability.
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DOI：
10.1007/s00223-011-9465-5
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发表时间：
2011-05
影响因子：
4.2
通讯作者：
Levine, Michael A.
中科院分区：
文献类型：
--
作者：
Jap, Tjin-Shing;Chiu, Chih-Yang;Niu, Dau-Ming;Levine, Michael A.
磷酸盐调节内肽酶同源物X连锁基因（PHEX）的突变导致最常见的低磷血症性佝偻病，即X连锁低磷血症性佝偻病（XLH），该基因编码一种参与骨矿化和肾磷酸盐重吸收的锌依赖性内肽酶。PHEX突变分布广泛，但在中国XLH患者中发现的突变很少。我们从9名生活在台湾的无关中国受试者（3男6女，年龄范围11-36岁）的白细胞中提取基因组DNA和总RNA。通过PCR从DNA中扩增PHEX基因，并将扩增产物直接测序。通过白细胞RNA的逆转录PCR进行表达研究。患者的血清FGF 23水平显著高于正常受试者（平均69.4 ± 18.8 vs. 27.2 ± 8.4 pg/mL，P < 0.005），9名患者中有8名患者的FGF 23水平升高。在9名患者中的5名中鉴定了PHEX基因的种系突变，包括新的c.1843 delA、供体剪接位点突变c.663+2delT和c.1899+ 2 T>A，以及两个先前报道的错义突变p.C733Y和p.G579R。这些数据扩展了中国汉族人PHEX基因突变的范围，并证实了台湾XLH的变异性。
Mutations in the phosphate-regulating endopeptidase homolog, X-linked, gene (PHEX), which encodes a zinc-dependent endopeptidase that is involved in bone mineralization and renal phosphate reabsorption, cause the most common form of hypophosphatemic rickets, X-linked hypophosphatemic rickets (XLH). The distribution of PHEX mutations is extensive, but few mutations have been identified in Chinese with XLH. We extracted genomic DNA and total RNA from leukocytes obtained from nine unrelated Chinese subjects (three males and six females, age range 11–36 years) who were living in Taiwan. The PHEX gene was amplified from DNA by PCR, and the amplicons were directly sequenced. Expression studies were performed by reverse-transcription PCR of leukocyte RNA. Serum levels of FGF23 were significantly greater in the patients than in normal subjects (mean 69.4 ± 18.8 vs. 27.2 ± 8.4 pg/mL, P < 0.005), and eight of the nine patients had elevated levels of FGF23. Germline mutations in the PHEX gene were identified in five of 9 patients, including novel c.1843 delA, donor splice site mutations c.663+2delT and c.1899+2T>A, and two previously reported missense mutations, p.C733Y and p.G579R. These data extend the spectrum of mutations in the PHEX gene in Han Chinese and confirm variability for XLH in Taiwan.
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影响因子：
4.2
作者：
Clausmeyer, S.;Hesse, V.;Raue, F.
通讯作者：
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影响因子：
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3.3
作者：
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通讯作者：
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