RESUMO
Hereditary conditions that affect tooth enamel in quantity and/or quality are called amelogenesis imperfecta (AI). AI can occur as an isolated condition or as a symptom of a syndrome. An OMIM search with the term "AI" yielded 79 result entries. Mutations in the same gene cause syndromic or non-syndromic AI, depending on the nature of the mutations. In this study, we recruited two AI families and performed mutational analysis using whole-exome sequencing. The proband of family 1, with hypoplastic pitted AI and mild localized atopic dermatitis, had compound heterozygous COL17A1 mutations (paternal NM_000494.4: c.3598G>T, p.Asp1200Tyr and maternal c.1700G>A, p.Gly567Glu). The proband of family 2, with hypoplastic pitted AI and Jervell and Lange-Nielsen syndrome, had a recurrent LAMB3 mutation (NM_000228.3: c.3463_3475del, p.(Glu1155Thrfs*51)) in addition to compound heterozygous mutations in the KCNQ1 gene.
RESUMO
The process of tooth formation is a series of reciprocal interactions between the ectoderm and mesoderm, and it is believed that many genetic factors are involved in this complex process. More than a dozen genes have been identified in non-syndromic tooth agenesis; however, the genetic etiology underlying tooth agenesis is not fully understood yet. In this study, we identified two novel LRP6 mutations in two non-syndromic oligodontia families. Both probands had 16 and 17 missing teeth in their permanent dentition. Mutational analysis identified a de novo frameshift mutation by a 1-bp insertion in exon 9 (NM_002336.2: c.1870dupA, p.(Met624Asnfs*29)) and a splicing donor site mutation in intron 8 (c.1762+2T>C). An in vitro splicing assay confirmed the deletion of exon 8, and the deletion would result in a frameshift. Due to the premature termination codons introduced by the frameshift, both mutant transcripts would be degraded by nonsense-mediated mRNA decay, resulting in haploinsufficiency.
