Enamel is the hardest biomineralised human tissue and its health is fundamental to normal tooth function.
Amelogenesis imperfecta (AI) is the name given to a clinically and genetically heterogeneous group of enamel biomineralisation defects that typically have Mendelian patterns of inheritance. Mutations in genes encoding enamel matrix proteins (AMELX & ENAM), enamel matrix modifying proteins (KLK4 & MMP20) and an intracellular protein of unknown function (FAM83H) are recognised to cause AI.
Objective: This study aims to describe the identification of a novel genetic locus for autosomal recessive AI.
Methods: A consanguineous Pakistani family with multiple affected individuals was ascertained. Family members were assessed through clinical examination and supporting investigations. DNA samples were collected following informed consent and ethics committee approval. Affymetrix 6.0 SNP chip genotyping was undertaken and analysed for blocks of homozygous SNPs, which were confirmed via microsatellite genotyping.
Results: A novel 14cM (10Mb) genetic locus for AI was identified on chromosome 15q21 with a maximum multipoint LOD score of 4.2.
Conclusion: Further investigations, including ongoing analyses to identify the causative genetic lesion, have the potential to give novel insights into pivotal events in enamel formation that are also potentially of relevance to other biomineralised tissues.
Funded by the Egyptian Government (WE) and The Wellcome Trust, grant number (082448).