Identification of genes related to susceptibility of periodontal diseases and establishment of gene diagnosis

低磷酸酶症（HOPS）是一种临床异质性遗传性疾病，其特征是骨骼矿化缺陷，组织非特异性碱性磷酸酶（TNSALP）活性缺乏和乳牙过早脱落。在以前的研究中，我们发现了一个患有严重牙周炎和儿童期HOPS的患者的TNSALP基因中的新的点突变（F310 L，V365 I）（J Periodontol，1999）。V365 I突变被认为是导致碱性磷酸酶（ALP）失活的原因（J Bone Miner Res，2002）。我们鉴定了突变体F310 L翻译的另一种ALP酶，并与正常人血清中的ALP进行了比较，转染F310 L的COS-1细胞和与F310 L和V365 I共转染的COS-1细胞的酶活性分别为67%和31%，野生型的酶活性为100%。在56℃加热5 min后，野生型、F310 L和V365 I的残余酶活分别约为未加热酶活的40.4%、21.7%和16.5%。患者血清ALP呈左旋咪唑不耐药型、热不稳定型及突变型。该突变体可能是除了突变体（V3651）之外的儿童型HOPS症状的表达的原因。

Hypophosphatasia (HOPS) is a clinically heterogeneous heritable disorder characterized by defective skeletal mineralization, deficiency of tissue-nonspecific alkaline phosphatase (TNSALP) activity and premature loss of deciduous teeth. In a previous study, we found novel point mutations (F310L, V365I) in the TNSALP gene of a patient with severe periodontitis and childhood HOPS (J Periodontol, 1999). The V365I mutation was considered responsible for the inactive alkaline phosphatase (ALP) enzyme (J Bone Miner Res, 2002). We have characterized another ALP enzyme translated from the mutant F310L and compared it with the ALP in the patient's serum in the presenl study.The COS-1 cells transfected with the F310L and co-transfected with F310L and V365I exhibited a level of 67% and 31%, respectively with the enzymatic activity of the wild-type taken as 100%. After heating at 56℃ for 5 min, the residual activity of the wild-type, F310L and V365I exhibited a level of approximately 40.4%, 21.7% and 16.5% of unheated enzymatic activily, respectively. The ALP of patient's serum showed levamisol-nonresistant and heat labile as well as mutant ALP. This mutant might be responsible for the expression of symptoms of the childhood-type HOPS, in addition lo the mutant (V3651).