Next generation sequencing reveals a novel nonsense mutation in MSX1 gene related to oligodontia

Bonczek, Ondřej; Bielik, Peter; Krejčí, Přemysl; Zeman, Tomáš; IzakovičováHollá, Lydie; Šoukalová, Jana; Vaněk, Jiřı́; Gerguri, Tereza; Balcar, Vladimír J.; Šerý, Omar

doi:10.1371/journal.pone.0202989

Cited by 24 publications

(14 citation statements)

References 49 publications

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“…The expression of Msx1 overlaps with that of Bmp4 in anterior and dental mesenchymal cells (Figure 5), and Msx1 is known as an upstream regulator of Bmp4 in dental mesenchymal cells 31 . Msx1 −/− mice exhibit placode invagination arrest in all molar germs, 35 and various types of mutations of MSX1 in humans cause oligodontia (see summary in Reference 41). Pax9 is expressed in molar and incisor dental mesenchymal cells, and Pax9 −/− mice show an early arrest in the formation of molars 34 and downregulation of Shh expression in incisor placodes in the mandibular process 42 .…”

Section: Discussionmentioning

confidence: 99%

Six1 is required for signaling center formation and labial‐lingual asymmetry in developing lower incisors

Takahashi

Ikeda

Ohmuraya

et al. 2020

Developmental Dynamics

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Background The structure of the mouse incisor is characterized by its asymmetric accumulation of enamel matrix proteins on the labial side. The asymmetric structure originates from the patterning of the epithelial incisor placode through the interaction with dental mesenchymal cells. However, the molecular basis for the asymmetric patterning of the incisor germ is largely unknown. Results A homeobox transcription factor SIX1 was shown to be produced in the mandibular mesenchyme, and its localization patterns changed dynamically during lower incisor development. Six1−/− mice exhibited smaller lower incisor primordia than wild‐type mice. Furthermore, Six1−/− mice showed enamel matrix production on both the lingual and labial sides and disturbed odontoblast maturation. In the earlier stages of development, the formation of signaling centers, the initiation knot and the enamel knot, which are essential for the morphogenesis of tooth germs, were impaired in Six1−/− embryos. Notably, Wnt signaling activity, which shows an anterior‐posterior gradient, and the expression patterns of genes involved in incisor formation were altered in the mesenchyme in Six1−/− embryos. Conclusion Our results indicate that Six1 is required for signaling center formation in lower incisor germs and the labial‐lingual asymmetry of the lower incisors by regulating the anterior‐posterior patterning of the mandibular mesenchyme.

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Section: Discussionmentioning

confidence: 99%

Six1 is required for signaling center formation and labial‐lingual asymmetry in developing lower incisors

Takahashi

Ikeda

Ohmuraya

et al. 2020

Developmental Dynamics

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“…It is possible that some genes are involved in the etiology only of severer TA cases (such as oligodontia), however, our sample size did not allow us to perform a stratified analysis, comparing only patients with oligodontia with control patients (without TA). In fact, mutations in MSX1, 26,27 PAX9 26 and AXIN2 28 were previously associated with oligodontia.…”

Section: Discussionmentioning

confidence: 99%

Genetic polymorphism in esr2 and risk of tooth agenesis

Marañón‐Vásquez

Spada

Omori

et al. 2019

CRORJ

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RESUMOIntrodução: A agenesia dentária (AD) é a ausência congênita de um ou mais dentes. Vários estudos vêm sugerindo o forte componente genético para essa condição. Objetivo: O presente estudo teve como objetivo avaliar se os polimorfismos genéticos nos genes que codificam os receptores de estrógeno (ESR1 e ESR2) estão associados à ocorrrência de AD isolada em uma amostra brasileira. Métodos: Radiografias panorâmicas de 142 pacientes ortodônticos foram avaliadas para determinar AD de dentes permanentes (excluindo terceiros molares). O DNA dos pacientes foi extraído das células da mucosa bucal contidas na saliva para avaliar polimorfismos genéticos em ESR1 (rs2234693 e rs9340799) e ESR2 (rs1256049 e rs4986938) por genotipagem usando a técnica de PCR em tempo real. Para análises estatísticas, associações entre as distribuições dos alelos e genótipos e a ocorrrência de AD foram avaliadas para cada polimorfismo genético, com um alfa estabelecido de 5%. Resultados: Treze pacientes tiveram pelo menos 1 dente congenitamente ausente. O número de dentes congenitamente ausentes variou de 1 a 11. Os polimorfismos genéticos rs2234693 e rs9340799 no ESR1 e rs1256049 no ESR2 não foram associados à AD (p > 0,05). Para o polimorfismo genético rs4986938 no ESR2, as distribuições dos genótipos e dos alelos foram estatisticamente diferentes entre os pacientes com e sem AD (p < 0,05). O genótipo CC e o alelo C estavam super-representados nos pacientes com AD. Conclusão: Houve associação entre o polimorfismo genético rs4986938 no ESR2 e a ocorrrência de AD. ABSTRACT Introduction:Tooth agenesis (TA) is the congenital absence of teeth. Several studies have proposed a strong genetic background for this condition. Aim: The present cross-sectional study aimed to evaluate whether genetic polymorphisms in the genes that code for estrogen receptors (ESR1 and ESR2) are associated with the presence of isolated TA in a Brazilian sample. Methods: Panoramic radiographs of 142 orthodontic patients were assessed to determine TA of permanent teeth (excluding third molars). DNA of patients was extracted from buccal cells from saliva to evaluate genetic polymorphisms in ESR1 (rs2234693 and rs9340799) and ESR2 (rs1256049 and rs4986938) by genotyping using the real-time PCR technique. For statistical analyses, associations between the distributions of the alleles and genotypes, and the ocurrence of TA were assessed for each genetic polymorphism, with an established alpha of 5%. Results: Thirteen patients had at least 1 congenital missing tooth. The number of congenitally missing teeth ranged from 1 to 11. The genetic polymorphisms rs2234693 and rs9340799 in ESR1 and rs1256049 in ESR2 were not associated with TA (p > 0.05). For the genetic polymorphism rs4986938 in ESR2, the genotype and allele distributions were significantly different between the patients with and without TA (p < 0.05). The CC genotype and the C allele were overrepresented in the TA patients. Conclusion: The genetic polymorphism rs4986938 in ESR2 was associated with the ocurrence of TA.

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“…In the event that a mutation can affect the gene function, we will proceed by analysing the occurrence of this mutation in relation to the mental disorders in the families being studied, in the same manner as we have done in the work on the genetics of oligodontia. 48 Then, all of the SNPs with P values exceeding the selected threshold and being approximately in linkage equilibrium with the others, will be used to calculate the PRS for each participant using the logistic regression model. The polygenic risk score uses an additive model to quantify an individual´s genetic loading for a disorder, as influenced by the presence of multiple risk alleles.…”

Section: Discussionmentioning

confidence: 99%

“…The technology described above is routinely used in our laboratories. 48,49 We will focus on the genes relevant to the mental disorders under study: ADRA2A, AKT1, BDNF, CCKAR, CHI3L1, CHRNA7, CLDN5, CNR1, COMT , CRFR1, CTXN3, DISC1, DPYSL2, DRD3, DTNBP1, EGF, GABRA1, GABRB2, GAD1, GRIK3, GRM3, HTR2A, HTR3A, IL10, MAOA, MAOB, MCHR1, MLC1, NEUROG1, NOS1, NOS1AP, NOTCH4, NPY, NRG1, NR3C1, OLIG2, OPMR1, PDE4B, PLA2G4A, PLXNA2, PPP3CC, PRODH, RELN, RGS4, RTN4, SLC6A4, SNAP25, SRR, SYN2, TNF, TP53, UFD1L, XBP1, YWHAE, ACE, TNF alpha, TGF beta, MTHFR, IL1, IL2, IL6, CRP, GSK3 and others according to the lists published by Schmidt-Kastner et al, Roussos et Haroutunian, Hosak and Jiang et al and according to our previous studies. [50][51][52][53][54][55][56][57] Epigenetic (miRNA) Assessment…”

Section: The Examination Of Reactivity To Stressmentioning

confidence: 99%

<p>Gene–Environment Interactions in Major Mental Disorders in the Czech Republic</p>

Látalová

Šerý

Hosakova

et al. 2020

NDT

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Background: Mental disorders affect about one-third of the human population, are typically chronic and significantly decrease the quality of life. Presently, the treatment of mental illnesses is far from adequate with a substantial proportion of the patients being pharmacoresistant and suffering from relapses. One of the reasons for this complicated situation is that we do not precisely know about the causes of mental disorders, so their treatment cannot be causal. The etiology of a mental disorder is typically based on a combination of molecular (genetic) and environmental factors. Aim: The aim of the project is to discover the gene-environment interactions (GxE) in a wide spectrum of mental disorders. Methods: The design of our study is innovative in the sense that we intend to study large groups of associated mental disorders as a whole instead of in isolation. This would enable us to map out the possible environmental causal factors in detail in relation to their character, magnitude and timing. The project also allows a study of genetics (including epigenetics and microbiomes) as well as the environment simultaneously. We plan on involving three study groups: the first group are patients suffering from schizophrenia or a mood disorder such as major depression, recurrent depressive disorder and bipolar affective disorder; the second group of patients have anxiety disorders; and the third group are healthy volunteers from the general population who are genetically unrelated. All of the study subjects will undergo the following assessments: a psychiatric examination, the identification of stressful life events with the aid of a questionnaire, the examination of their reaction to stress, genetic and epigenetic (microRNA) assessments and the analysis of oral and gut microbiome. Conclusion: We expect that some of the genetic as well as environmental factors in the studied mental disorders are shared, while some others are specific. We also expect that the GxE (gene-environment interaction) in schizophrenic and affective disorders will be different from the GxE in anxiety disorders and that the GxE in the studied mental disorders will differ generally from the GxE in healthy volunteers. Our results can help in the prevention and individualized treatment of a range of mental disorders.

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Next generation sequencing reveals a novel nonsense mutation in MSX1 gene related to oligodontia

Cited by 24 publications

References 49 publications

Six1 is required for signaling center formation and labial‐lingual asymmetry in developing lower incisors

Six1 is required for signaling center formation and labial‐lingual asymmetry in developing lower incisors

Genetic polymorphism in esr2 and risk of tooth agenesis

<p>Gene–Environment Interactions in Major Mental Disorders in the Czech Republic</p>

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