De novo mutation of PHEX in a type 1 diabetes patient
De novo mutation of PHEX in a type 1 diabetes patient
复制标题
1 型糖尿病患者 PHEX 新生突变
DOI：
10.1515/jpem-2015-0399
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发表时间：
2016-05-01
影响因子：
1.4
通讯作者：
Hu, Ji
中科院分区：
文献类型：
--
作者：
Fang, Chen;Li, Hui;Hu, Ji
本文报道了一个四代中国汉族家系中X染色体第4外显子（c.442C>T）的一个新的错义突变（PHEX）。先证者及4名家系成员经临床确诊为X连锁低磷血症性佝偻病（XLH），是一种以肾性磷酸盐消耗、维生素D代谢异常和骨矿化异常为特征的显性遗传性疾病。先证者为半合子，家系4名女性成员为杂合子基因型。这一发现是通过对该家族的PHEX基因的外显子和内含子-外显子边界进行完全测序而得出的。该突变导致S141残基从Ser变为Phe，Ser在人、小鼠、大鼠、牛和鸡中完全保守。PolyPhen-2软件对突变的分析表明，它可能是有害的。先证者同时被诊断为1型糖尿病（T1 D），本文讨论了XLH与糖尿病表型的关系。
Abstract A new missense mutation on the X chromosome (PHEX) at exon 4(c.442C>T) in a 4-generation Chinese Han pedigree is reported. The proband and four family members were clinically identified as the X-linked hypophosphatemic rickets (XLH) which is a dominant inherited disorder characterized by renal phosphate wasting, aberrant vitamin D metabolism, and abnormal bone mineralization. The proband is identified as hemizygous with the four female family members to be heterozygous genotypes. The discovery was made through the complete sequencing of the exons and the intron-exon boundaries of the PHEX gene of this family. The mutation caused the S141 residue to change to Phe from Ser which is perfectly conserved among humans, mice, rats, cows and chickens. PolyPhen-2 software analysis of the mutation indicated it was probably damaging. The proband was also diagnosed with type 1 diabetes (T1D) and the relationship between XLH and diabetes phenotypes was discussed in the paper.