Mutation in kallikrein 4 causes autosomal recessive hypomaturation amelogenesis imperfecta

Abstract

Serine protease functionality is based on nucleophilic attack of a targeted peptidic bond by a serine. The serine protease superfamily is extremely diverse and includes proteases such as plasminogen, prostatin, hepsin, the kallikrein family ( KLK genes clustered on chromosome 19.13), and a recently discovered cluster of tryptic-like serine proteases located on human chromosome 16p13.1,2 Serine protease mutations have been reported as causative in only a few autosomal recessive human hereditary conditions, which produce diverse pathological conditions.3,4 We report the first human kallikrein mutation and describe its association with a rare autosomal recessive form of amelogenesis imperfecta. The amelogenesis imperfectas are a clinically and genetically heterogeneous group of disorders characterised by faulty development of the tooth enamel due to hypoplasia or hypomineralisation.5 The amelogenesis imperfecta phenotypes vary widely depending on the specific gene involved, the location and type of mutation, and the corresponding putative change at the protein level.6,7 The amelogenesis imperfecta enamel defects can be broadly divided into hypoplastic (enamel crystallites do not grow to the correct length) and hypomineralised (crystallites fail to grow in thickness or width) phenotypes. The prevalence of amelogenesis imperfecta varies in different countries (ranging from 1 in 700 in Sweden to 1 in 14 000 in the United States) suggesting allele frequency differences between populations.8–11 Amelogenesis imperfecta can be inherited as an autosomal dominant, autosomal recessive, or X-linked Mendelian trait. While autosomal dominant amelogenesis imperfecta types are most common in the United States and Europe, autosomal recessive amelogenesis imperfecta types are more common in the Middle East.8,10,11 Dental enamel is the most highly mineralised tissue in the human body with 85% of its volume occupied by highly organised carbonate substituted hydroxyapatite crystals.12 These crystallites are packed into a highly ordered decussating prism …