Mutational spectrum of<i>FAM83H</i>: the C-terminal portion is required for tooth enamel calcification

Lee, Sook-Kyung; Hu, Jan C.‐C.; Bartlett, John D.; Lee, Kyung-Eun; Lin, Brent; Simmer, James P.; Kim, Jung-Wook

doi:10.1002/humu.20789

Cited by 58 publications

(58 citation statements)

References 7 publications

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“…Previous studies proposed that FAM83H encode a nonsecreted protein due to the absence of a signal peptide [Kim et al, 2008]. In the present study, by running SWISS-MODEL and CPHmodels-3.0, the Nterminal of FAM83H favor a template 1byr, which is the first crystal structure of a PLD family member.…”

Section: Discussionmentioning

confidence: 97%

“…The expression of FAM83H in many tissues suggests that it functions in many cells throughout the body [Kim et al, 2008;Lee et al, 2009]. The predicted quite different structures for the N-and C-terminals of FAM83H indicate that the two parts could play different roles in different cell types.…”

Section: Discussionmentioning

confidence: 99%

“…Also, mutations in a poorly characterized WDR72 gene were newly identified to cause autosomal recessive hypomaturation AI [ElSayed et al, 2009]. Recently, the etiology of hypocalcified AI has been revealed to be associated with mutations in the FAM83H gene, which is deduced to encode a nonsecreted protein [Kim et al, 2008]. A total of 17 mutations in FAM83H have so far been identified to cause hypocalcified AI in different populations [Kim et al, 2008;Lee et al, 2008;Hart et al, 2009;Hyun et al, 2009;Wright et al, 2009;El-Sayed et al, 2010;Lee et al, 2011].…”

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confidence: 99%

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Molecular Characterization of Amelogenesis Imperfecta in Chinese Patients

Song

Wang

Zhang

et al. 2012

Cells Tissues Organs

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Background: Mutations in 6 genes have been identified as being part of the etiology of amelogenesis imperfecta (AI) with various phenotypes in an isolated condition. Among them the FAM83H gene is the major contributor to the etiology of AI with unknown function. Objective: This study aims to determine the phenotypic and molecular characterization of Chinese AI patients and to analyze the structure and function of the FAM83H protein. Methods: We enrolled 6 hypocalcified AI and 3 hypoplastic AI families from the Chinese population. Mutation analysis was performed by amplifying and sequencing all exons including intron-exon borders for FAM83H and ENAM genes. Structural modeling and function analysis on the FAM83H protein were carried out by bioinformatic processing. Results: No obvious anterior open bite was observed in all the investigated individuals. Five mutations (c.906T>G, c.924dupT, c.973C>T, c.1354C>T and c.2029C>T) in the C-terminal of the FAM83H gene were revealed, respectively, in 5 out of 6 hypocalcified AI families, and a splicing mutation c.534 + 1G>A in the ENAM gene was identified in 1 out of 3 hypoplastic AI families. Structural models of the N- and C-terminal regions of FAM83H were generated by homology modeling. The predicted structure of the FAM83H N-terminal shows resemblance to that of glycosyltransferases with GT-A folds, and the predicted structure of the FAM83H C-terminal possesses similarity to type I collagen protein. Conclusions: To our knowledge, this is the first report of AI with specific molecular variations in families of Chinese descent. Our study provides new insights into the structure and function of the FAM83H protein.

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Section: Discussionmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 99%

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confidence: 99%

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Molecular Characterization of Amelogenesis Imperfecta in Chinese Patients

Song

Wang

Zhang

et al. 2012

Cells Tissues Organs

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“…Another report analyzed the known candidate genes ENAM, AMBN, AMELX, MMP20, KLK4, and amelotin (AMNT) in two Brazilian families by PCR and sequencing and excluded the participation of these genes in the hypomineralized AI phenotype (Santos et al 2007). Surprisingly, at the beginning of 2008, two studies carried out by the same group of researchers reported 6 mutations in the FAM83H gene, found in region 8q24.3, which is responsible for hypocalcified ADAI (Lee et al 2008a). With the recent work of Hart et al (2009), Wright et al (2009), Hyun et al (2009), and El-Sayed et al (2010, the number of mutations in the FAM83H gene has increased to 16 ( Table 1).…”

Section: Phenotype-genotype Correlations In Autosomally Inherited Casesmentioning

confidence: 94%

“…To date, 9 mutations have been reported in the enamelin gene (Table 1) (Rajpar et al 2001;Mardh et al 2002;Kida et al 2002;Hart et al 2003b;Kim et al 2005a;Ozdemir et al 2005a;Gutiérrez et al 2007;Kang et al 2009); 1 mutation has been reported in DLX3, which is responsible for the ADAI cases associated with taurodontism (Dong et al 2005); and 16 mutations have been reported in the recently nominated FAM83H gene. This series of mutations within these three genes are all associated with ADAI of the hypocalcified type (Table 1) Lee et al 2008a;Hart et al 2009, Wright et al 2009Hyun et al 2009;El-Sayed et al 2010).…”

Section: Autosomally Inherited Typesmentioning

confidence: 96%

Defining a New Candidate Gene for Amelogenesis Imperfecta: From Molecular Genetics to Biochemistry

et al. 2010

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Amelogenesis imperfecta is a group of genetic conditions that affect the structure and clinical appearance of tooth enamel. The types (hypoplastic, hypocalcified, and hypomature) are correlated with defects in different stages of the process of enamel synthesis. Autosomal dominant, recessive, and X-linked types have been previously described. These disorders are considered clinically and genetically heterogeneous in etiology, involving a variety of genes, such as AMELX, ENAM, DLX3, FAM83H, MMP-20, KLK4, and WDR72. The mutations identified within these causal genes explain less than half of all cases of amelogenesis imperfecta. Most of the candidate and causal genes currently identified encode proteins involved in enamel synthesis. We think it is necessary to refocus the search for candidate genes using biochemical processes. This review provides theoretical evidence that the human SLC4A4 gene (sodium bicarbonate cotransporter) may be a new candidate gene.

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FAM83 family oncogenes are broadly involved in human cancers: an integrative multi‐omics approach

et al. 2017

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The development of novel targeted therapies for cancer treatment requires identification of reliable targets. FAM83 (‘family with sequence similarity 83’) family members A, B, and D were shown recently to have oncogenic potential. However, the overall oncogenic abilities of FAM83 family genes remain largely unknown. Here, we used a systematic and integrative genomics approach to investigate oncogenic properties of the entire FAM83 family members. We assessed transcriptional expression patterns of eight FAM83 family genes (FAM83A‐H) across tumor types, the relationship between their expression and changes in DNA copy number, and the association with patient survival. By comparing the gene expression levels of FAM83 family members in cancers from 17 different tumor types with those in their corresponding normal tissues, we identified consistent upregulation of FAM83D and FAM83H across the majority of tumor types, which is largely driven by increased DNA copy number. Importantly, we found also that a higher expression level of a signature of FAM83 family members was associated with poor prognosis in a number of human cancers. In breast cancer, we found that alterations in FAM83 family genes correlated significantly with TP53 mutation, whereas significant, but inverse correlation was observed with PIK3CA and CDH1 (E‐cadherin) mutations. We also identified that expression levels of 55 proteins were significantly associated with alterations in FAM83 family genes including a decrease in GATA3, ESR1, and PGR proteins in tumors with alterations in FAM83. Our results provide strong evidence for a critical role of FAM83 family genes in tumor development, with possible relevance for therapeutic target development.

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Mutational spectrum ofFAM83H: the C-terminal portion is required for tooth enamel calcification

Cited by 58 publications

References 7 publications

Molecular Characterization of Amelogenesis Imperfecta in Chinese Patients

Molecular Characterization of Amelogenesis Imperfecta in Chinese Patients

Defining a New Candidate Gene for Amelogenesis Imperfecta: From Molecular Genetics to Biochemistry

FAM83 family oncogenes are broadly involved in human cancers: an integrative multi‐omics approach

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