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

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. Furthermore, 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 ?anking intron sequences of the ALPL gene were ampli?ed 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.V7YfsX18) 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 praline. Both of the two mutations were not detected in 50 normal controls and not reported previously. After searching PubMed and the TNSALP gene mutations database, both of the two mutations were 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.

Key words: Hypophosphatasia（HPP）, Tissue non-specific alkaline phosphatase (TNSALP), ALPL , Mutation