Publications by authors named "Sylvia A Frazier-Bowers"

14 Publications

  • Page 1 of 1

American Association of Orthodontists Foundation Rapid Assessment of Evidence: Accelerated teeth movement.

Am J Orthod Dentofacial Orthop 2021 03 31;159(3):396-397.e3. Epub 2020 Dec 31.

UNC Orthodontics, Adams School of Dentistry, University of North Carolina, Chapel Hill, NC.

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http://dx.doi.org/10.1016/j.ajodo.2020.11.013DOI Listing
March 2021

A novel nonsense PTH1R variant shows incomplete penetrance of primary failure of eruption: a case report.

BMC Oral Health 2019 11 15;19(1):249. Epub 2019 Nov 15.

Department of Orthodontics, School of Dentistry, University of North Carolina, Chapel Hill, NC, USA.

Background: Aim of this work was to describe a rare inheritance pattern of Primary Failure of Eruption (PFE) in a small family with incomplete penetrance of PFE and a novel nonsense PTH1R variant.

Case Presentation: The proband, a 26 year-old man with a significant bilateral open-bite, was diagnosed with PFE using clinical and radiographic characteristics. DNA was extracted from the proband and his immediate family using buccal swabs and the entire PTH1R coding sequence was analyzed, revealing a novel heterozygous nonsense variant in exon 7 of PTH1R (c.505G > T). This variant introduces a premature stop codon in position 169, predicted to result in the production of a truncated and non-functional protein. This variant has never been reported in association with PFE and is not present in the Genome Aggregation Database (gnomAD). Interestingly, the c.505G > T variant has also been identified in the unaffected mother of our proband, suggesting incomplete penetrance of PFE.

Conclusions: In this study, we report a new PTH1R variant that segregates in an autosomal dominant pattern and causes PFE with incomplete penetrance. This underlines the diagnostic value of a thorough clinical and genetic analysis of all family members in order to estimate accurate recurrence risks, identify subtle clinical manifestations and provide proper management of PFE patients.
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http://dx.doi.org/10.1186/s12903-019-0944-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6858648PMC
November 2019

Craniofacial characterization of Marfan Syndrome.

Orthod Craniofac Res 2019 May;22 Suppl 1:56-61

Department of Orthodontics, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.

Objective: The morbidity and mortality associated with the Marfan Syndrome (MFS) warrant timely diagnosis and intervention that can improve long-term prognosis. The aim of this study was to test the hypothesis that a distinct craniofacial morphology exists for patients with MFS that can be described quantitatively and qualitatively.

Methods: Subjects with a positive diagnosis of MFS were recruited for this study (N = 36). Craniofacial anthropometric measurements were made on each subject and compared to established norms of age- and sex-matched controls using z-scores calculated for measurements of MFS patients. Lateral and frontal photographs were obtained to make qualitative assessments and describe facial features of subjects, and a clinical examination was completed to document occlusal relationships.

Results: The subjects were primarily female (58%) ranging in age between 4 and 57 years (mean age 10.7 ± 6.0 years). Comparison of craniofacial measurements revealed that for 10 of the 12 measurements, ≥65% of the study population had a z-score of ± 2 and fell within the normal range for facial dimension. For 2 of the 12 measurements, over half of the subjects fell outside of the normal range (z-score < -2 or > 2) for facial dimension. Specifically, the majority of participants resided in the supernormal category for biocular width and the subnormal category for width of the face. Photographic assessment revealed retrognathia (54%) and down-slanting palpebral fissures (62%) were most prevalent in MFS patients.

Conclusion: Our data suggest there are quantitative differences in the facial morphology of patients with MFS when compared to a control population.
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http://dx.doi.org/10.1111/ocr.12295DOI Listing
May 2019

Preface to COAST 2018 Innovators' Workshop: Bridging the biology and technology gap in orthodontics and craniofacial care.

Orthod Craniofac Res 2019 May;22 Suppl 1:5-7

Department of Orthodontics, School of Dentistry, Oregon Health and Science University, Portland, Oregon.

Objective: A third focused workshop explored how to transfer novel findings into clinical orthodontic practice.

Setting And Sample Population: Participants met at the Scottsdale Plaza Resort, 12-16 September 2018 for the Consortium for Orthodontic Advances in Science and Technology 2018 Innovators' Workshop. Thirty speakers and four lunch-hour focus group leaders shared and exchanged information with approximately 45 registered attendees.

Material And Methods: This Innovators' Workshop was organized according to five themed sessions which covered: (a) The relevance of genetics, biology and environment to therapeutic outcomes; (b) Application of bioinformatics in craniofacial research; (c) Regeneration with and for orthodontic treatment; (d) Technology in precision orthodontics; and (e) Muscle, joint, and airway: Growth, function and pain.

Results: The papers that comprise this supplemental issue exemplify the important outcomes of the 2018 COAST Workshop. In addition, matters identified as important needs include improved understanding of neural, skeletal and muscle tissue crosstalk in early craniofacial growth; standardized methods for three-dimensional radiographic and surface landmark and reference plane identification, measurements and serial superimpositioning techniques for use in the clinic; sharing and making available existing data sets (eg, cone beam computed tomography images, genotype-phenotype data); evidence of the usefulness and effectiveness of new devices; guidelines of what to measure to characterize the airway; more information about the influences of the soft tissues on craniofacial morphology; and information about effective digital work flows applied to clinical and educational settings.

Conclusions: Progress in bridging the biology-technology gap has identified new needs for improvements in orthodontics and craniofacial care.
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http://dx.doi.org/10.1111/ocr.12303DOI Listing
May 2019

Primary failure of eruption: Clinical and genetic findings in the mixed dentition.

Angle Orthod 2018 May 29;88(3):275-282. Epub 2018 Jan 29.

Objective: To test the hypothesis that mutations in the parathyroid hormone 1 receptor ( PTH1R) include effects in both primary and permanent teeth.

Materials And Methods: DNA was extracted from saliva samples of 29 patients (8 familial and 21 sporadic) who presented with clinical evidence of infraoccluded teeth, and their unaffected relatives (N = 22). Sequencing followed by mutational analysis of the coding regions of PTH1R gene was completed for all individuals (N = 29).

Results: Eight of 29 cases revealed a heterozygous pathogenic variant in the PTH1R gene; five of eight variants represented distinct mutations based on comparison with the dbSNP, HGMD, and ESP databases. One mutation (c.1765 T>C p.Trp89Arg) was found to segregate within a family (n = 3). In silico analyses for all variants revealed a putative pathogenic effect. A genotype-phenotype correlation was reported as defined by a functional mutation in PTH1R and corresponding effects on one or more posterior teeth only; unilateral or bilateral involvement, infraoccluded primary teeth.

Conclusions: Novel mutations were reported in the PTH1R gene that included PFE-affected primary molars, thus providing the basis for using a genetic diagnostic tool for early diagnosis leading to proper management.
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http://dx.doi.org/10.2319/062717-430.1DOI Listing
May 2018

Genetic Disorders of Dental Development: Tales from the Bony Crypt.

Curr Osteoporos Rep 2017 02;15(1):9-17

Department of Oral Health Sciences, Faculty of Dentistry, University of British Columbia, JBM-184 - 2199 Wesbrook Mall, Vancouver, BC, V6T 1Z3, Canada.

Purpose Of Review: The ebb and flow of genetic influence relative to the understanding of craniofacial and dental disorders has evolved into a tacit acceptance of the current genetic paradigm. This review explores the science behind craniofacial and dental disorders through the lens of recent past and current findings and using tooth agenesis as a model of advances in craniofacial genetics.

Recent Findings: Contemporary studies of craniofacial biology takes advantage of the technological resources stemming from the genomic and post-genomic eras. Emerging data highlights the role of key genes and the epigenetic landscape controlling these genes, in causing dentofacial abnormalities. We also report here a novel Glu78FS MSX1 mutation in one family segregating an autosomal dominant form of severe tooth agenesis as an illustration of an evolving theme, i.e., different mutations in the same gene can result in a spectrum of dentofacial phenotypic severity. The future of clinical therapeutics will benefit from advances in genetics and molecular biology that refine the genotype-phenotype correlation. Indeed, the past century suggests a continued convergence of genetic science in the practice of clinical dentistry.
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http://dx.doi.org/10.1007/s11914-017-0342-7DOI Listing
February 2017

Simultaneous sequencing of oxidized methylcytosines produced by TET/JBP dioxygenases in Coprinopsis cinerea.

Proc Natl Acad Sci U S A 2014 Dec 18;111(48):E5149-58. Epub 2014 Nov 18.

Division of Signaling and Gene Expression, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037; Department of Pharmacology and Moores Cancer Center, University of California, San Diego, La Jolla, CA 92093

TET/JBP enzymes oxidize 5-methylpyrimidines in DNA. In mammals, the oxidized methylcytosines (oxi-mCs) function as epigenetic marks and likely intermediates in DNA demethylation. Here we present a method based on diglucosylation of 5-hydroxymethylcytosine (5hmC) to simultaneously map 5hmC, 5-formylcytosine, and 5-carboxylcytosine at near-base-pair resolution. We have used the method to map the distribution of oxi-mC across the genome of Coprinopsis cinerea, a basidiomycete that encodes 47 TET/JBP paralogs in a previously unidentified class of DNA transposons. Like 5-methylcytosine residues from which they are derived, oxi-mC modifications are enriched at centromeres, TET/JBP transposons, and multicopy paralogous genes that are not expressed, but rarely mark genes whose expression changes between two developmental stages. Our study provides evidence for the emergence of an epigenetic regulatory system through recruitment of selfish elements in a eukaryotic lineage, and describes a method to map all three different species of oxi-mCs simultaneously.
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http://dx.doi.org/10.1073/pnas.1419513111DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4260599PMC
December 2014

Establishing the diagnostic criteria for eruption disorders based on genetic and clinical data.

Am J Orthod Dentofacial Orthop 2013 Aug;144(2):194-202

Department of Orthodontics, School of Dentistry, University of North Carolina, Chapel Hill, NC, USA.

Introduction: Proper diagnosis and management of eruption disturbances remains challenging but is critical to a functional occlusion. The objective of this study was to establish definitive criteria to differentiate and diagnose eruption disorders, specifically primary failure of eruption (PFE) and ankylosis.

Methods: Sixty-four affected persons were placed into 3 cohorts: PFE diagnosed through confirmed PTH1R mutation (n = 11), PFE diagnosed based on clinical criteria (n = 47), and ankylosis diagnosed based on clinical criteria (n = 6). These groups were assessed to identify clinical features that differentiate PFE and ankylosis.

Results: Ninety-three percent of the subjects in the genetic and clinical PFE cohorts combined (n = 58) and 100% in the genetic PFE cohort had at least 1 infraoccluded first permanent molar. Additionally, a novel functional PTH1R mutation, 1092delG, was identified and linked to PFE in the deciduous dentition.

Conclusions: An infraoccluded, supracrestal first molar is a hallmark of PFE, often involving both arches in the permanent or deciduous dentition, and with unilateral or bilateral affection, infraoccluded second premolar or second molar, and multiple affected adjacent teeth. Our results further suggest that PFE and ankylosis might be clinically indistinguishable without knowledge of prior trauma, treatment history, genetic information, or obliteration of the periodontal ligament space.
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http://dx.doi.org/10.1016/j.ajodo.2013.03.015DOI Listing
August 2013

The etiology of eruption disorders - further evidence of a 'genetic paradigm'

Semin Orthod 2010 Sep;16(3):180-185

Department of Orthodontics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, Tel: (919) 966-2762, ,

The clinical spectrum of tooth eruption disorders includes both syndromic and non-syndromic problems ranging from delayed eruption to a complete failure of eruption. A defect in the differential apposition/resorption mechanism in alveolar bone can cause conditions such as tooth ankylosis, primary failure of eruption, failure of eruption due to inadequate arch length and canine impaction. As our knowledge of the molecular events underlying normal tooth eruption has increased, so too has our understanding of clinical eruption disorders. The recent finding that one gene, parathyroid hormone receptor 1 (PTH1R), is causative for familial cases of primary failure of eruption (PFE) suggests that other disturbances in tooth eruption may have a genetic etiology. In this report, we evaluated the current terminology (ankylosis, PFE, secondary retention, etc.) used to describe non-syndromic eruption disorders, in light of this genetic discovery. We observed that some individuals previously diagnosed with ankylosis were subsequently found to have alterations in the PTH1R gene, indicating the initial misdiagnosis of ankylosis and the necessary re-classification of PFE. We further investigated the relationship of the PTH1R gene, using a network pathway analysis, to determine its connectivity to previously identified genes that are critical to normal tooth eruption. We found that PTH1R acts in a pathway with genes such as PTHrP that have been shown to be important in bone remodeling, hence eruption, in a rat model. Thus, recent advances in our understanding of normal and abnormal tooth eruption should allow us in the future to develop a clinical nomenclature system based more on the molecular genetic cause of the eruption failures versus the clinical appearance of the various eruption disorders.
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http://dx.doi.org/10.1053/j.sodo.2010.05.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2933797PMC
September 2010

Primary failure of eruption and PTH1R: the importance of a genetic diagnosis for orthodontic treatment planning.

Am J Orthod Dentofacial Orthop 2010 Feb;137(2):160.e1-7; discussion 160-1

Department of Orthodontics, University of North Carolina, Chapel Hill, NC, USA.

Introduction: Primary failure of eruption (PFE) is characterized by nonsyndromic eruption failure of permanent teeth in the absence of mechanical obstruction. Recent studies support that this dental phenotype is inherited and that mutations in PTH1R genes explain several familial cases of PFE. The objective of our study was to investigate how genetic analysis can be used with clinical diagnostic information for improved orthodontic management of PFE.

Methods: We evaluated a family (n = 12) that segregated an autosomal dominant form of PFE with 5 affected and 7 unaffected persons. Nine available family members (5 male, 4 female) were enrolled and subsequently characterized clinically and genetically.

Results: In this family, PFE segregated with a novel mutation in the PTH1R gene. A heterozygous c.1353-1 G>A sequence alteration caused a putative splice-site mutation and skipping of exon 15 that segregated with the PFE phenotype in all affected family members.

Conclusions: A PTH1R mutation is strongly associated with failure of orthodontically assisted eruption or tooth movement and should therefore alert clinicians to treat PFE and ankylosed teeth with similar caution-ie, avoid orthodontic treatment with a continuous archwire.
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http://dx.doi.org/10.1016/j.ajodo.2009.10.019DOI Listing
February 2010

Primary failure of eruption: further characterization of a rare eruption disorder.

Am J Orthod Dentofacial Orthop 2007 May;131(5):578.e1-11

Department of Orthodontics, School of Dentistry, University of North Carolina, Chapel Hill, NC 27599-7450, USA.

Introduction: Posterior open bite has several possible causes, including primary failure of eruption (PFE) that affects all teeth distal to the most mesial involved tooth, mechanical failure of eruption (MFE) (primarily ankylosis) that affects only the involved tooth or teeth, and soft-tissue interferences with eruption (other).

Methods: Radiographs and other clinical records for 97 cases of failure of posterior eruption submitted for consultation were analyzed to further characterize PFE and distinguish it from MFE.

Results: Of the 97 cases, 38 were judged to be clear-cut PFE; 19 were diagnosed as MFE; 32 were classified as indeterminate failure because they were too young to be certain of the distinction between PFE and MFE; and 8 were placed in the "other" category. Two subtypes of PFE were observed. In type 1, eruption failure occurred at or near the same time for all teeth in an affected quadrant. In type 2, a gradient of the time of failure was present, so that some further development of the teeth posterior to the most mesial affected tooth was observed before eruption failure. A family history of eruption problems was noted in 10 of the 38 PFE subjects (26%), and a pedigree analysis was done for 4 families. This was consistent with autosomal dominant transmission.

Conclusions: The distinction between PFE and MFE is clinically important because it determines whether all posterior teeth, or only individual affected teeth, will not respond to orthodontic force. Certain diagnosis often requires progress radiographs so that the pattern of eruption of teeth distal to the most mesial affected tooth can be observed.
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http://dx.doi.org/10.1016/j.ajodo.2006.09.038DOI Listing
May 2007

A longitudinal study of incremental expansion using a mandibular lip bumper.

Angle Orthod 2003 Aug;73(4):396-400

Department of Orthodontics, Dental Branch, University of Texas Health Science Center at Houston, 77030, USA.

A retrospective study using models was performed to evaluate the incremental expansion that occurred during mandibular lip bumper therapy in 44 adolescent patients. The purpose was to determine whether expansion occurs evenly between appointments or whether it attenuates with treatment time. Dental cast measurements were made for arch width and arch length. Treatment duration was broken into near-equal time segments and compared. Results showed that about 50% of the total expansion achieved occurred within about the first 100 days. Forty percent of the total amount of expansion occurred during the next 200 days, with only about 10% of the total expansion occurring after the first 300 days. It is unnecessary to have the appliance in place for longer than 300 days. The percentage of expansion that occurred at each time segment was not related to whether the patient had concomitant maxillary expansion.
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http://dx.doi.org/10.1043/0003-3219(2003)073<0396:ALSOIE>2.0.CO;2DOI Listing
August 2003

Mutational analysis of families affected with molar oligodontia.

Connect Tissue Res 2002 ;43(2-3):296-300

Department of Orthodontics, University of Texas Health Science Center-Dental Branch, Houston, Texas 77030, USA.

Oligodontia, the congenital absence of six or more permanent teeth, is a common developmental anomaly of human dentition whose genetic basis is poorly understood. We recently reported a nonsyndromic form of oligodontia involving mostly all permanent molars in a large kindred, caused by a frameshift mutation in exon 2 of the human PAX9 gene [3]. To better understand the genotype/phenotype correlation in non-syndromic familial oligodontia, we identified additional families with a similar pattern of molar oligodontia. We hypothesize that molar oligodontia is due to allelic heterogeneity involving different mutations in PAX9. To test this hypothesis, we performed pedigree analysis followed by mutational analysis. Pedigree analysis revealed that the oligodontia trait is inherited in an autosomal dominant fashion. Mutational analysis of PAX9 thus far excludes the presence of the previously identified frameshift mutation.
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http://dx.doi.org/10.1080/03008200290000961DOI Listing
April 2003