title: Phenotypic variation in FAM83H-associated amelogenesis imperfecta.
abstract: FAM83H gene mutations are associated with autosomal-dominant hypocalcified amelogenesis imperfecta (ADHCAI), which is typically characterized by enamel having normal thickness and a markedly decreased mineral content. This study tested the hypothesis that there are phenotype and genotype associations in families with FAM83H-associated ADHCAI. Seven families segregating ADHCAI (147 individuals) were evaluated. Phenotyping included clinical, radiographic, histological, and biochemical studies, and genotyping was by mutational analysis. Multiple novel FAM83H mutations were identified, including two 2-bp-deletion mutations, the first non-nonsense mutations identified. Craniofacial deviation from normal was more prevalent in the affected individuals. Affected individuals having truncating FAMH3H mutations of 677 or fewer amino acids presented a generalized ADHCAI phenotype, while those having mutations capable of producing a protein of at least 694 amino acids had a unique and previously unreported phenotype affecting primarily the cervical enamel. This investigation shows that unique phenotypes are associated with specific FAM83H mutations.
authors.affiliation: Dept. of Pediatric Dentistry, School of Dentistry, CB #7450 Brauer Hall, UNC Chapel Hill, NC 27599, USA. tim_wright@dentistry.unc.edu
authors.forename: J T
authors.initials: JT
authors.lastname: Wright
authors.forename: S
authors.initials: S
authors.lastname: Frazier-Bowers
authors.forename: D
authors.initials: D
authors.lastname: Simmons
authors.forename: K
authors.initials: K
authors.lastname: Alexander
authors.forename: P
authors.initials: P
authors.lastname: Crawford
authors.forename: S T
authors.initials: ST
authors.lastname: Han
authors.forename: P S
authors.initials: PS
authors.lastname: Hart
authors.forename: T C
authors.initials: TC
authors.lastname: Hart
mesh_terms: D000567:Amelogenesis Imperfecta / Q000150:complications / Q000235:genetics* / Q000378:metabolism; D001483:Base Sequence; D002508:Cephalometry; D018389:Codon, Nonsense / Q000235:genetics; D019465:Craniofacial Abnormalities / Q000150:complications / Q000235:genetics*; D003746:Dental Enamel Proteins / Q000378:metabolism; D006801:Humans; D008445:Maxillofacial Development / Q000235:genetics; D010375:Pedigree; D011506:Proteins / Q000235:genetics*; D017384:Sequence Deletion / Q000235:genetics
chemical_list: D018389:Codon, Nonsense; D003746:Dental Enamel Proteins; C527308:FAM83H protein, human; D011506:Proteins