Genetic evaluations of Chinese patients with odontohypophosphatasia resulting from heterozygosity for mutations in the tissue-non-specific alkaline phosphatase gene

// Jia Wan 1, * , Li Zhang 2, * , Tang Liu 1 and Yewei Wang 3 1 Department of Orthopaedics, The Second Xiangya Hospital of Central South University, Changsha 410011, P.R.China 2 Department of Endocrinology, The Fifth Central Hospital of Tianjin, Tianjin 300192, P.R.China 3 Department of Hemotology, The Second Xiangya Hospital of Central South University, Changsha 410011, P.R.China * Jia Wan and Li Zhang are the co-first authors Correspondence to: Tang Liu, email: liutang1204@csu.edu.cn Yewei Wang, email: wangyeweixy@hotmail.com Keywords: hypophosphatasia, odonto-hypophosphatasia, gene mutation, premature exfoliation of primary teeth, TNSALP Received: January 24, 2017 Accepted: May 07, 2017 Published: May 23, 2017 ABSTRACT Background : Hypophosphatasia is a rare heritable metabolic disorder characterized by defective bone and tooth mineralization accompanied by a deficiency of tissue-non-specific (liver/bone/kidney) isoenzyme of alkaline phosphatase activity, caused by a number of loss-of-function mutations in the alkaline phosphatase liver type gene. We seek to explore the clinical manifestations and identify the mutations associated with the disease in a Chinese odonto- hypophosphatasia family. Results : The proband and his younger brother affected with premature loss of primary teeth at their 2-year-old. They have mild abnormal serum alkaline phosphatase and 25-hydroxy vitamin D values, but the serum alkaline phosphatase activity of their father, mother and grandmother, who showed no clinical symptoms of hypophosphatasia, was exhibited significant decreased. In addition to premature loss of primary teeth, the proband and his younger brother showed low bone mineral density, X-rays showed that they had slight metaphyseal osteoporosis changes, but no additional skeletal abnormalities. Deoxyribonucleic acid sequencing and analysis revealed a single nucleotide polymorphism c.787T>C (p.Y263H) in exon 7 and/or a novel mutation c.-92C>T located at 5’UTR were found in the affected individuals. Materials and Methods : We examined all individuals of an odonto- hypophosphatasia family by clinical and radiographic examinations as well as laboratory assays. Furthermore, all 12 exons and the exon-intron boundaries of the alkaline phosphatase liver type gene were amplified and directly sequenced for further analysis and screened for mutations. Conclusion : Our present findings suggest the single nucleotide polymorphism c.787T>C and c.-92C>T should be responsible for the odonto- hypophosphatasia disorders in this family.