Dataset Information

Identification of a Novel FAM83H Mutation and Management of Hypocalcified Amelogenesis Imperfecta in Early Childhood.

ABSTRACT: Amelogenesis imperfecta (AI) is a heterogeneous group of rare genetic disorders affecting amelogenesis during dental development. Therefore, the molecular genetic etiology of AI can provide information about the nature and progress of the disease. To confirm the genetic etiology of AI in a Korean family with an autosomal dominant inheritance, pedigree and mutational analyses were performed. DNA was isolated from the participating family members and whole-exome sequencing was performed with the DNA sample of the father of the proband. The identified mutation was confirmed by Sanger sequencing. The mutational analysis revealed a novel nonsense mutation in the FAM83H gene (NM_198488.5: c.1363C > T, p.(Gln455*)), confirming autosomal dominant hypocalcified AI. Full-mouth restorative treatments of the affected children were performed after the completion of the deciduous dentition. Early diagnosis of AI can be useful for understanding the nature of the disease and for managing the condition and treatment planning.

SUBMITTER: Song JS

PROVIDER: S-EPMC8947619 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Identification of a Novel <i>FAM83H</i> Mutation and Management of Hypocalcified Amelogenesis Imperfecta in Early Childhood.

Song Ji-Soo JS Lee Yejin Y Shin Teo Jeon TJ Hyun Hong-Keun HK Kim Young-Jae YJ Kim Jung-Wook JW

Children (Basel, Switzerland) 20220318 3

Amelogenesis imperfecta (AI) is a heterogeneous group of rare genetic disorders affecting amelogenesis during dental development. Therefore, the molecular genetic etiology of AI can provide information about the nature and progress of the disease. To confirm the genetic etiology of AI in a Korean family with an autosomal dominant inheritance, pedigree and mutational analyses were performed. DNA was isolated from the participating family members and whole-exome sequencing was performed with the D ...[more]

PMID: 35327801

Similar Datasets

Project description:Autosomal dominant hypocalcified amelogenesis imperfecta (ADHCAI; OMIM #130900) is a genetic disorder exhibiting severe hardness defects and reduced fracture toughness of dental enamel. While the condition is nonsyndromic, it can be associated with other craniofacial anomalies, such as malocclusions and delayed or failed tooth eruption. Truncation mutations in FAM83H (OMIM *611927) are hitherto the sole cause of ADHCAI. With human genetic studies, Fam83h knockout and mutation-knock-in mouse models indicated that FAM83H does not serve a critical physiologic function during enamel formation and suggested a neomorphic mutation mechanism causing ADHCAI. The function of FAM83H remains obscure. FAM83H has been shown to interact with various isoforms of casein kinase 1 (CK1) and keratins and to mediate organization of keratin cytoskeletons and desmosomes. By considering FAM83H a scaffold protein to anchor CK1s, further molecular characterization of the protein could gain insight into its functions. In this study, we characterized 9 kindreds with ADHCAI and identified 3 novel FAM83H truncation mutations: p.His437*, p.Gln459*, and p.Glu610*. Some affected individuals exhibited hypoplastic phenotypes, in addition to the characteristic hypocalcification enamel defects, which have never been well documented. Failed eruption of canines or second molars in affected persons was observed in 4 of the families. The p.Glu610* mutation was located in a gap area (amino acids 470 to 625) within the zone of previously reported pathogenic variants (amino acids 287 to 694). In vitro pull-down studies with overexpressed FAM83H proteins in HEK293 cells demonstrated an interaction between FAM83H and SEC16A, a protein component of the COP II complex at endoplasmic reticulum exit sites. The interaction was mediated by the middle part (amino acids 287 to 657) of mouse FAM83H protein. Results of this study significantly extended the phenotypic and genotypic spectrums of FAM83H-associated ADHCAI and suggested a role for FAM83H in endoplasmic reticulum-to-Golgi vesicle trafficking and protein secretion (dbGaP phs001491.v1.p1).

Dataset Information

Identification of a Novel FAM83H Mutation and Management of Hypocalcified Amelogenesis Imperfecta in Early Childhood.

Publications

Identification of a Novel <i>FAM83H</i> Mutation and Management of Hypocalcified Amelogenesis Imperfecta in Early Childhood.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets