Mutation Screening of ENAM, KLK4, MMP20 and FAM83H Genes among the Members of Five Iranian Families Affected with Autosomal Recessive Hypoplastic Amelogenesis Imperfecta

Amelogenesis Imperfectas (AIs) are clinically and genetically heterogeneous conditions characterized by a wide range of clinical features. These abnormalities of enamel formation are categorized into three main groups, hypoplastic, hypomaturation and hypocalcified with different modes of inheritance such as autosomal recessive (AR), autosomal dominant (AD) and X-lined recessive (XLR). In spite of the fact that frequent studies have explained the histological features of AIs, our knowledge regarding the molecular etiology of the affected enamel is not adequate. Up to now, different loci have been suggested to associate with the causation of AIs. Several genetic mutations including enamelin (ENAM), amelogenin (AMELX), ameloblastin (AMBN), tuftelin (TUFT1), kallikrein 4 (KLK4), matrix metalloproteinase 20 (MMP20) and family with sequence similarity 83, member H (FAM83H) have been suggested to play critical roles in the pathogenesis of these disorders. Therefore, the aim of this investigation was to study of mutation screening in ENAM, KLK4, MMP20 and FAM83H genes, responsible for AIs development in five Iranian families in which the probands were diagnosed with autosomal recessive hypoplastic amelogenesis imperfecta (ARHAI). Genomic DNA was extracted from probands and exon/intron boundaries of afore-mentioned genes were amplified by PCR and subjected to direct sequencing. We could not detect any mutation in the studied genes however; two different novel polymorphisms including T18515C and G18504A were identified in the intron 4 of MMP20 in the probands of two families. Our findings support the notion that different genes may be involved in the development of amelogenesis imperfectas.