Fang Chen, Li Hui, Li Xiaozhen, Xiao Wenjin, Huang Yun, Cai Wu, Yang Yi, Hu Ji
J Pediatr Endocrinol Metab. 2016 May 1;29(5):621-6. doi: 10.1515/jpem-2015-0399.
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.
报道了一个四代中国汉族家系中X染色体（PHEX）第4外显子（c.442C>T）上的一个新错义突变。先证者和四名家庭成员经临床诊断为X连锁低磷性佝偻病（XLH），这是一种显性遗传病，其特征为肾性磷酸盐 wasting、异常的维生素D代谢和异常的骨矿化。先证者被鉴定为半合子，四名女性家庭成员为杂合子基因型。该发现是通过对该家系PHEX基因的外显子和内含子-外显子边界进行全序列测序得出的。该突变导致S141残基由Ser变为Phe，这在人类、小鼠、大鼠、牛和鸡中是完全保守的。对该突变进行的PolyPhen-2软件分析表明它可能具有损害性。先证者还被诊断患有1型糖尿病（T1D），本文讨论了XLH与糖尿病表型之间的关系。
