Sawai Hideaki, Kanazawa Nozomi, Tsukahara Yuki, Koike Kazunori, Udagawa Hideo, Koyama Koji, Mornet Etienne
Laboratory of Developmental Biology and Reproduction, Institute for Advanced Medical Sciences, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan.
Prenat Diagn. 2003 Sep;23(9):743-6. doi: 10.1002/pd.696.
Hypophosphatasia is an inherited disorder characterized by defective bone mineralization and deficiency of tissue nonspecific alkaline phosphatase (TNSALP) activity. This disorder is caused by various mutations in the TNSALP gene. We report here hypophosphatasia in two siblings, both of them severely affected by the perinatal (lethal) type.
We diagnosed the first infant by clinical and radiologic manifestations, and laboratory findings. Laboratory findings were characterized by deficiency of serum alkaline phosphatase. Both parents and the second infant were then analyzed by molecular techniques.
The radiograph of the first infant showed severe hypomineralization of the skeleton. Molecular analysis of the second infant showed that this condition was caused by a homozygous single T nucleotide deletion at cDNA number 1559 (1559delT). Both parents were heterozygous carriers for this mutation, although they were not consanguineous.
This mutation has been frequently found in Japanese hypophosphatasia patients, but this is the first observation of a homozygous deletion. This report shows that homozygosity for the 1559delT mutation of the TNSALP gene results in a severe lethal phenotype.
低磷酸酯酶症是一种遗传性疾病，其特征为骨矿化缺陷和组织非特异性碱性磷酸酶（TNSALP）活性缺乏。该疾病由TNSALP基因的各种突变引起。我们在此报告两名患有低磷酸酯酶症的兄弟姐妹，他们均受到围产期（致死）型的严重影响。
我们通过临床和影像学表现以及实验室检查结果诊断了第一名婴儿。实验室检查结果的特征是血清碱性磷酸酶缺乏。然后对父母和第二名婴儿进行分子技术分析。
第一名婴儿的X线片显示骨骼严重矿化不足。对第二名婴儿的分子分析表明，这种情况是由cDNA编号1559处的纯合单T核苷酸缺失（1559delT）引起的。尽管父母并非近亲结婚，但他们都是该突变的杂合携带者。
这种突变在日本低磷酸酯酶症患者中经常发现，但这是首次观察到纯合缺失。本报告表明，TNSALP基因1559delT突变的纯合性会导致严重的致死表型。
