台灣地區罹患低磷酸鹽血性佝僂症家族之PHEX基因突變研究

Abstract

低磷血性佝僂症是因為腎臟無機磷酸鹽傳送障礙導致無機磷酸鹽流失及低磷血症 的疾患。本研究收集18 名低磷血性佝僂症及其家人的血液進行PHEX 基因的突變分析， 結果於其中13 名患童發現PHEX 基因突變，這些突變中有5 名為無意義突變，4 名為缺 失，2 名為插入及2 名為誤義突變。其中83% PHEX 基因突變導致PHEX 蛋白質產物的 截短，而且69%的突變為這些家庭內無中生有的新突變。本研究顯示PHEX 基因突變所 導致的性聯低磷血性佝僂症為台灣地區低磷血性佝僂症最常見的原因，而此種突變大多 數為無中生有的新突變。

Hypophosphatemic rickets consists of a group of disorders characterized by a defect in renal phosphate transport resulting in phosphate wasting and hypophosphatemia. Eighteen unrelated Taiwanese patients with hypophosphatemic rickets and their families were enrolled for the mutational analysis of their PHEX gene in this study. Mutations of PHEX gene was detected in 13 out of 18 patients (72%) with hypophosphatemic rickets. These mutations include 5 nonsense mutations, 4 deletions, 2 insertions and 2 missense mutations. The majority (83%) of these mutations are predicted to result in truncation of the PHEX protein product and 69% of these mutations have arisen de novo. Our data revealed that X-linked hypophosphatemic rickets due to mutations of PHEX gene is the most common cause of hypophosphatemic rickets in Taiwan and most of such mutations of PHEX gene occurred de novo.