Open AccessPhenotypic Variation in FAM83H-associated Amelogenesis Imperfecta
Author(s) -
J. Timothy Wright,
Sylvia A. FrazierBowers,
Darrin Simmons,
Keisha N. Alexander,
P. J. M. Crawford,
Sejin Han,
Patricia Hart,
Thomas C. Hart
Publication year - 2009
Publication title -
journal of dental research
Language(s) - English
Resource type - Journals
eISSN - 1544-0591
pISSN - 0022-0345
DOI - 10.1177/0022034509333822
Subject(s) - amelogenesis imperfecta , phenotype , craniofacial , biology , genetics , nonsense mutation , gene , mutation , genotyping , genotype , enamel paint , missense mutation , medicine , dentistry
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.