Ultrastructural analysis of the teeth affected by amelogenesis imperfecta resulting from FAM83H mutations and review of the literature

Zhang, Chenzheng; Song, Yaling; Bian, Zhuan

doi:10.1016/j.oooo.2014.09.002

Cited by 23 publications

(26 citation statements)

References 29 publications

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“…Polymorphisms might have a slight effect on amelogenesis, mainly regarding the enamel mineralization/maturation, because we have demonstrated here the significant association of SNP rs7821494 in the FAM83H gene with the genetic predisposition to MIH. Although our results reinforce the evidence regarding the influence of the FAM83H gene on amelogenesis, the mechanisms and functions of the FAM83H protein during enamel and dentine formation remain unclear [Zhang et al, 2015].…”

Section: Discussionsupporting

confidence: 76%

“…The FAM83H protein is required for proper dental enamel calcification [Kim et al, 2008]. Recently, Zhang et al [2015], showed that FAM83H could influence enamel biomineralization and dentine formation, and they reviewed studies that identified different mutations in the FAM83H gene associated with autosomal dominant hypocalcified amelogenesis imperfecta (ADHCAI) [Zhang et al, 2015]. There are at least 14 different registered mutations in the FAM83H gene associated with ADHCAI (http://omim.…”

Section: Discussionmentioning

confidence: 99%

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Family-Based Genetic Association for Molar-Incisor Hypomineralization

Jeremias

Pierri²,

Souza³

et al. 2016

Caries Res

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Despite some evidence of genetic and environmental factors on molar-incisor hypomineralization (MIH), its aetiology remains unclear. This family-based genetic association study aimed more comprehensively to investigate the genetic carriage potentially involved in MIH development. DNA was obtained from buccal cells of 391 individuals who were birth family members of 101 Brazilian nuclear families. Sixty-three single nucleotide polymorphisms (SNPs) were investigated in 21 candidate genes related to amelogenesis using the TaqMan™ OpenArray™ Genotyping platform. All SNPs were genotyped in 165 birth family members unaffected by MIH, 96 with unknown MIH status and 130 affected individuals (50.7% with severe MIH). Association analysis was performed by the transmission/disequilibrium test (TDT), and statistical results were corrected using the false discovery rate. Significant results were obtained for SNPs rs7821494 (FAM83H gene, OR = 3.7; 95% CI = 1.75-7.78), rs34367704 (AMBN gene, OR = 2.7; 95% CI = 1.16-6.58), rs3789334 (BMP2 gene, OR = 2.9; 95% CI = 1.34-6.35), rs6099486 (BMP7 gene, OR = 2.2; 95% CI = 1.14-4.38), rs762642 (BMP4 gene, OR = 2.3; 95% CI = 1.38-3.65), rs7664896 (ENAM gene, OR = 2.1; 95% CI = 1.19-3.51), rs1711399 (MMP20 gene, OR = 0.4; 95% CI = 0.20-0.72), rs1711423 (MMP20 gene, OR = 2.1; 95% CI = 1.18-3.61), rs2278163 (DLX3 gene, OR = 2.8; 95% CI = 1.26-6.41), rs6996321 (FGFR1 gene, OR = 2.7; 95% CI = 1.20-5.88), and rs5979395 (AMELX gene, OR = 11.7; 95% CI = 1.63-84.74). Through this family-based association study, we concluded that variations in genes related to amelogenesis were associated with the susceptibility to develop MIH. This result is in agreement with the multifactorial idea of the MIH aetiology, but further studies are necessary to investigate more thoroughly the factors that could influence MIH.

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Section: Discussionsupporting

confidence: 76%

Section: Discussionmentioning

confidence: 99%

Family-Based Genetic Association for Molar-Incisor Hypomineralization

Jeremias

Pierri²,

Souza³

et al. 2016

Caries Res

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“…In this study, the investigated AI patients showed various degrees of crowding, cross-bite, and tooth impaction, but no signs of obvious anterior open bite. It is notable that the nonsense mutation (c.973 C > T, p.R325X) identified in family 4 has been reported previously to cause hypocalcified AI in one Korean and two Chinese families, and is presumably an AI mutation hotspot in Asian population 6, 8, 28 . According to previous reports, several affected individuals in the Korean pedigree exhibited an anterior open bite; however, those in the Chinese pedigrees showed no signs of severe malocclusion.…”

Section: Discussionmentioning

confidence: 80%

Novel FAM83H mutations in patients with amelogenesis imperfecta

Wang

Qin

et al. 2017

Sci Rep

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Amelogenesis imperfecta (AI), characterized by a deficiency in the quantity and/or quality of dental enamel, is genetically heterogeneous and phenotypically variable. The most severe type, hypocalcified AI, is mostly caused by truncating mutations in the FAM83H gene. This study aimed to identify genetic mutations in four Chinese families with hypocalcified AI. We performed mutation analysis by sequencing the candidate FAM83H gene. Three novel mutations (c.931dupC, p.V311Rfs*13; c.1130_1131delinsAA, p.S377X; and c.1147 G > T, p.E383X) and one previously reported mutation (c.973 C > T, p.R325X) in the last exon of FAM83H gene were identified. Furthermore, constructs expressing Green fluorescent protein (GFP)-tagged wild-type and three novel mutant FAM83Hs were transfected into rat dental epithelial cells (SF2 cells). Wild-type FAM83H-GFP was localized exclusively in the cytoplasm, especially in the area surrounding the nucleus, while the mutant FAM83H-GFPs (p.V311Rfs*13, p.S377X, and p.E383X) were localized predominantly in the nucleus, with lower levels in the cytoplasm.

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“…Analysis of teeth from individuals with FAM83H mutations identified defects in enamel rods, especially at the DEJ, with increased organic content within the enamel (El-Sayed et al, 2010; Zhang et al, 2015a). …”

Section: The Genetics Of Amelogenesis Imperfectamentioning

confidence: 99%

Amelogenesis Imperfecta; Genes, Proteins, and Pathways

et al. 2017

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Amelogenesis imperfecta (AI) is the name given to a heterogeneous group of conditions characterized by inherited developmental enamel defects. AI enamel is abnormally thin, soft, fragile, pitted and/or badly discolored, with poor function and aesthetics, causing patients problems such as early tooth loss, severe embarrassment, eating difficulties, and pain. It was first described separately from diseases of dentine nearly 80 years ago, but the underlying genetic and mechanistic basis of the condition is only now coming to light. Mutations in the gene AMELX, encoding an extracellular matrix protein secreted by ameloblasts during enamel formation, were first identified as a cause of AI in 1991. Since then, mutations in at least eighteen genes have been shown to cause AI presenting in isolation of other health problems, with many more implicated in syndromic AI. Some of the encoded proteins have well documented roles in amelogenesis, acting as enamel matrix proteins or the proteases that degrade them, cell adhesion molecules or regulators of calcium homeostasis. However, for others, function is less clear and further research is needed to understand the pathways and processes essential for the development of healthy enamel. Here, we review the genes and mutations underlying AI presenting in isolation of other health problems, the proteins they encode and knowledge of their roles in amelogenesis, combining evidence from human phenotypes, inheritance patterns, mouse models, and in vitro studies. An LOVD resource (http://dna2.leeds.ac.uk/LOVD/) containing all published gene mutations for AI presenting in isolation of other health problems is described. We use this resource to identify trends in the genes and mutations reported to cause AI in the 270 families for which molecular diagnoses have been reported by 23rd May 2017. Finally we discuss the potential value of the translation of AI genetics to clinical care with improved patient pathways and speculate on the possibility of novel treatments and prevention strategies for AI.

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Ultrastructural analysis of the teeth affected by amelogenesis imperfecta resulting from FAM83H mutations and review of the literature

Cited by 23 publications

References 29 publications

Family-Based Genetic Association for Molar-Incisor Hypomineralization

Family-Based Genetic Association for Molar-Incisor Hypomineralization

Novel FAM83H mutations in patients with amelogenesis imperfecta

Amelogenesis Imperfecta; Genes, Proteins, and Pathways

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