Detection of a Novel Mutation in X-linked Amelogenesis Imperfecta

Abstract

Amelogenesis imperfecta (AI) is a heterogeneous group of inherited disorders of defective enamel formation. The major protein involved in enamel formation, amelogenin, is encoded by a gene located at Xp22.1-Xp22.3. This study investigated the molecular defect producing a combined phenotype of hypoplasia and hypomineralization in a family with the clinical features and inheritance pattern of X-linked amelogenesis imperfecta (XAI). Genomic DNA was prepared from buccal cells sampled from family members. The DNA was subjected to the polymerase chain-reaction (PCR) in the presence of a series of oligonucleotide primers designed to amplify all 7 exons of the amelogenin gene. Cloning and sequencing of the purified amplification products identified a cytosine deletion in exon VI at codon 119. The deletion resulted in a frameshift mutation, introducing a premature stop signal at codon 126, producing a truncated protein lacking the terminal 18 amino acids. Identifying mutations assists our understanding of the important functional domains within the gene, and finding another novel mutation emphasizes the need for family-specific diagnosis of amelogenesis imperfecta.

Deletion of Slc26a1 and Slc26a7 Delays Enamel Mineralization in Mice

“…The genes responsible for AI in human patients include AMELX, AMBN, ENAM, MMP20, KLK4, WDR72, FAM83H, LAMB3, ITGB6, and SLC24A4 , and current evidence tends to support a single-gene origin for many AI cases (Aldred et al, 1992; Lench et al, 1994; Lagerstrom-Fermer and Landegren, 1995; Lagerstrom-Fermer et al, 1995; Collier et al, 1997; MacDougall et al, 1997; Hart et al, 2000, 2003, 2004, 2009; Kindelan et al, 2000; Mardh et al, 2002; Kim et al, 2004, 2005, 2008, 2013; El-Sayed et al, 2009; Wright et al, 2009; Poulter et al, 2014a,b,c; Wang S. et al, 2014; Wang S. K. et al, 2014; Herzog et al, 2015). Our data from the double-mutant animals ( Slc26a1 −/− / Slc26a7 −/− ) suggest that polygenic etiologic factors might also be involved in the pathogenesis of AI/AI-like symptoms, which increases the complexity of genetic diagnosis for enamel disorders.…”

Rat wct mutation prevents differentiation of maturation-stage ameloblasts resulting in hypo-mineralization in incisor teeth

“…In humans, amelogenin genes are localized to the X (AMELX) and Y (AMELY) chromosomes. Mutational analyses have shown that X-linked AI (AIH1), a phenotypically diverse hereditary disorder aVecting enamel development, is caused by deletions or point mutations in human AMELX Kindelan et al 2000;Ravassipour et al 2000;Hart et al 2002;Kim et al 2004). Amelogenin-null mice displayed distinctly abnormal teeth with white, chalky discoloration, and the amelogenin-null phenotype revealed that amelogenins are essential for the organization of crystal pattern and regulation of enamel thickness (Gibson et al 2001; Bartlett et al 2006).…”

MiR-153 Regulates Amelogenesis by Targeting Endocytotic and Endosomal/lysosomal Pathways–Novel Insight into the Origins of Enamel Pathologies

“…Among all the enamel diseases, AI is the most severe inherited disorder, which inflicts great suffering and treatment cost on patients. To date, identified genes responsible for AI include AMELX, AMBN, ENAM, MMP20, KLK4, FAM83H and SLC24A4 ; however, it is estimated that mutations in these genes account for less than half of the documented cases of AI404142434445464748495051525354555657585960. Based on the present study, miR-153 overloading during enamel maturation induces significant hypomineralization—AI-like signs–in affected animal teeth (Fig.…”