Identification of the Mutations in the Tissue-nonspecific Alkaline Phosphatase Gene in Two Chinese Families with Hypophosphatasia

Background and Aims osphatasia is a genetic disorder characterized by defective bone and tooth mineralization and a deficiency of serum and bone alkaline phosphatase activity. To date, few studies have identified gene mutations in Chinese patients with hypophosphatasia. We sought to characterize the clinical manifestations and identify the mutations associated with the disease in Chinese hypophosphatasia patients. s exons and the exon-intron boundaries of the ALPL gene were amplified and directly sequenced in two probands from unrelated Chinese families. The mutation sites were identified in other unaffected members of these two families and 100 healthy controls. s ily 1, the proband displayed one novel splice site mutation, c.298-1G>A, which consisted of a homozygous G>A transition at nucleotide 298-1 in intron 4. The proband’s mother displayed the heterozygous G/A ALPL gene mutation, but her father was identified as G/G homozygous. A paternity test ruled out false paternity and therefore confirmed that this splicing mutation occurred de novo either in the paternal germline or in the early development of the patient. In family 2, the proband revealed a novel missense mutation (c.1271T>C) in exon 11, which resulted in p.Val424Ala in the mature ALPL polypeptide. Furthermore, c.298-1G>A and c.1271T>C mutations were not found in unaffected family members of these two Chinese families and 100 unrelated controls. sions udy shows that the novel de novo splicing mutation c.298-1G>A in intron 4 and the missense mutation c.1271T>C in exon 11 of the ALPL gene are responsible for hypophosphatasia in some Chinese patients.