基础医学与临床2011，Vol.31Issue(3)：263-267,5.
低磷酸酶血症一家系组织非特异性碱性磷酸酶(TNSALP)基因突变分析
Detection of two novel mutations in the tissue-nonspecific alkaline phosphatase (TNSALP) gene in a patient with hypophosphatasia
摘要
Abstract
Objective In this study the clinical and genetic characteristics of a Chinese boy with childhood hypophosphatasia was analyzed, and genetic mechanism and genotype-phenotype correlation discussed. Methods According to the clinical manifestation and laboratory findings, the preliminary diagnose of hypophosphatasia was given to the patient. Genomic DNA was extracted from peripheral blood leukocytes of the patient, his family members and 50 ethnically matched, unrelated controls. All the 12 exons and flanking intron sequences of the ALPL gene were ampli fled by PCR. Direct DNA sequence analysis was performed by automated DNA sequencing. Results Sequence analysis of PCR products in the proband indicated that HPP originated from the heterozygous mutations c. 18delA and c. G407C of the ALPL gene. The c. 18delA mutation results in frameshift and premature termination of the translation. The predicted truncated protein (p. V7YfsXI8) lacks almost all the crucial regions for the enzyme function and bone mineralization. The nucleotide transition G ＞ C at position 407 resulted in an amino acid exchange from arginine 136 to proline. Both of the two mutations were not detected in 50 normal controls and not reported previously. Pedigree analysis showed that the c. 18delA and c. G407C had been inherited from the proband's mother and father, respectively. In addition, his grandmother was also found carring the mutation c. G407C. According to the family pedigree, the disease was transmitted as an autosomal recessive trait. Conclusion The two novel mutations c. 18delA and c. G407C in ALPL gene may provide new insights into the pathological mechanism and clinical manifestation of this rare disease.关键词
低磷酸酶血症(HPP)/组织非特异性碱性磷酸酶(TNSALP)/ALPL基因/突变Key words
hypophosphatasia(HPP)/ tissue non-specific alkaline phosphatase (TNSALP)/ ALPL gene/ mutation分类
医药卫生引用本文复制引用
刘海娟,孟迅吾,周学瀛,李梅,邢小平,夏维波,余卫,聂敏,王鸥,姜艳,胡莹莹..低磷酸酶血症一家系组织非特异性碱性磷酸酶(TNSALP)基因突变分析[J].基础医学与临床,2011,31(3):263-267,5.基金项目
中华医学会骨质疏松和骨矿盐疾病分会科研基金 （）
国家自然科学基金科学部主任基金(30440074) （30440074）
国家科技支撑计划项目(2008BAl58802) （2008BAl58802）
