Genetic and developmental disorders of the oral mucosa: Epidemiology; molecular mechanisms; diagnostic criteria; management

AbstractTranscription factor p63 is a key regulator of epidermal keratinocyte proliferation and differentiation. In humans mutations in p63 cause several developmental disorders with defects of ectoderm-derived structures including the epidermis. The underlying molecular mechanisms of these mutations however remain unclear. Here we characterized the transcriptome and epigenome from EEC syndrome patients carrying mutations in the p63 DNA-binding domain. The transcriptome of p63 mutant keratinocytes deviated from the normal epidermal cell identity. Epigenomic analyses showed that the deregulated gene expression in p63 mutant keratinocytes resulted from an altered enhancer landscape contributed by loss of p63-bound active enhancers and by unexpected gain of enhancers. The gained enhancers in mutant keratinocytes were frequently bound by deregulated transcription factors such as RUNX1. Reversing RUNX1 overexpression partially rescued deregulated gene expression as well as the enhancer distribution. Our findings support the pivotal role of p63 in controlling the enhancer landscape of epidermal keratinocytes and identify a novel mechanism whereby p63 DNA-binding mutations associated with EEC syndrome rewire the enhancer landscape and affect epidermal cell identity.

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Psychotic spectrum disorders in childhood

Srpski arhiv za celokupno lekarstvo ◽

10.2298/sarh0810555p ◽

2008 ◽

Vol 136 (9-10) ◽

pp. 555-558

Author(s):

Smiljka Popovic-Deusic ◽

Milica Pejovic-Milovancevic ◽

Saveta Draganic-Gajic ◽

Olivera Aleksic-Hil ◽

Dusica Lecic-Tosevski

Keyword(s):

Diagnostic Criteria ◽

Pervasive Developmental Disorders ◽

Developmental Disorders ◽

Psychotic Disorders ◽

Classification Systems ◽

Infancy And Childhood ◽

Icd 10 ◽

Long Time ◽

Early Infantile Autism ◽

The Right

For a long time, there was a strong belief of existing continuity between childhood-onset psychoses and adult psychoses. Important moment in understanding psychotic presentations during infancy and childhood is Kanner's description of early infantile autism. Later studies of Rutter and Kolvin, as well as new classification systems, have delineated pervasive developmental disorders from all other psychotic disorders in childhood. But clinical experience is showing that in spite of existence of the group of pervasive developmental disorders with subgroups within it and necessary diagnostic criteria there are children with pervasive symptoms, who are not fulfilling all necessary diagnostic criteria for pervasive developmental disorder. Therefore, in this paper we are discussing and pointing at psychotic spectrum presentations in children, which have not the right place in any existing classification system (ICD-10, DSM-IV).

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Molecular Mechanisms of Aroma Persistence: From Noncovalent Interactions Between Aroma Compounds and Oral Mucosa to Metabolization of Aroma Compounds by Saliva and Oral Cells

10.26434/chemrxiv.14595606 ◽

2021 ◽

Author(s):

Carolina Muñoz-Gonzalez ◽

Marine Brulé ◽

Christophe Martin ◽

Gilles Feron ◽

Francis Canon

Keyword(s):

Oral Mucosa ◽

Molecular Mechanisms ◽

Ex Vivo ◽

Noncovalent Interactions ◽

Aroma Compounds ◽

Integral Approach ◽

Exhaled Air ◽

Oral Cells ◽

Novel Model

Aroma persistence plays a major role in the liking and wanting of orally consumed products (food, dental toiletries, tobacco, drugs, etc.). Here, we use an integral approach including ex vivo experiments using a novel model of oral mucosa and saliva in well controlled conditions as well as in vivo dynamic instrumental and sensory experiments. Ex vivo experiments show the ability of the mucosal pellicle, the thin layer of salivary proteins covering the oral mucosa, to interact with aroma compounds, as well as the ability of oral cells and saliva to metabolize carbonyl aroma compounds. In vivo evaluation of the exhaled air and perception of individuals after aroma sample consumption confirm ex vivo findings in a more real context. Thus, aroma compounds susceptible to be metabolized by saliva and oral cells show a lower aroma persistence than non metabolized compounds, for which other mechanisms such as the adsorption at the surface of the oral mucosa (mucosal pellicle) as a function of their hydrophobicity are involved. Thus, we argue that the physiological aspects occurring during the oral processing, and especially, metabolization of aroma compounds, have to be considered when studying the phenomenon of aroma persistence.

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Field Trials of the 1987 Draft of Chapter V (F) of ICD-10

The British Journal of Psychiatry ◽

10.1192/s0007125000295597 ◽

1988 ◽

Vol 152 (S1) ◽

pp. 33-37 ◽

Cited By ~ 6

Author(s):

Jack D. Burke

Keyword(s):

Mental Health ◽

Diagnostic Criteria ◽

Study Design ◽

Field Trial ◽

Developmental Disorders ◽

International Classification Of Diseases ◽

Field Trials ◽

Classification Of Diseases ◽

Icd 10

IntroductionThis paper will review the major objectives and study design of the Field Trials of the draft chapter on Mental Behavioural and Developmental Disorders in the tenth revision of the International Classification of Diseases (ICD-10), now in preparation. The text used in this Field Trial is the Clinical Descriptions and Diagnostic Guidelines, which is more elaborate than the Short Glossary for this chapter that will be published in the main volume of ICD-10. The text for the former will be published together with the Diagnostic Criteria for Research and other parts of the WHO family of instruments relevant to mental health.

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Molecular players in the development and maintenance of mesencephalic dopamine systems

Acta Neuropsychiatrica ◽

10.1017/s0924270800036206 ◽

1999 ◽

Vol 11 (2) ◽

pp. 71-73

Author(s):

J.P.H. Burbach ◽

P. Cazorla ◽

M.P. Smidt

Keyword(s):

Brain Development ◽

Developmental Disorders ◽

Molecular Mechanisms ◽

Neural Progenitor Cells ◽

Cellular Proliferation ◽

Movement Control ◽

Proliferation And Differentiation ◽

Novel Therapeutic Strategies ◽

External Signals ◽

Mesencephalic Dopamine

Several psychiatric diseases are considered to be neuro-developmental disorders. Amongst these are schizophrenia and autism, in which genetic and environmental components have been indicated. In these disorders intrinsic molecular mechanisms of brain development may be deranged due to genetic predispositions, or modified by external influences. Brain development is a delicate process of well-tuned cellular proliferation and differentiation of multipotent neural progenitor cells driven by spatiotemporal cues. One of the fundamental mechanisms is the interaction between external signals, e.g. growth factors, and internal regulators, e.g. transcription factors. An important transmitter system involved in behavioural and affective functions relevant for psychiatric disorders is the mesencephalic dopamine (DA) system. The mesencephalic DA system is organized in two anatomically and functionally different systems. DA neurons in the ventral tegmental area project to the mesolimbic system and are mostly related to control of behaviour. It has been implicated in drug addiction and affective disorders like dipolar disorder and schizophrenia. The dopamine system of the substantia nigra (nigro-striatal pathway) is implicated in movement control. Degeneration of this system, as in Parkinson's disease, or altered function in tardive dyskinesia have highlighted its importance in human disease. Recent findings in molecular neurobiology have provided the first clues to molecular mechanisms involved in developing and mature DA neurons. These may have clinical implications in novel therapeutic strategies.

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Dissection of molecular mechanisms underlying speech and language disorders

Applied Psycholinguistics ◽

10.1017/s0142716405050095 ◽

2005 ◽

Vol 26 (1) ◽

pp. 111-128 ◽

Cited By ~ 10

Author(s):

SIMON E. FISHER

Keyword(s):

Developmental Disorders ◽

Molecular Mechanisms ◽

Language Disorder ◽

Speech And Language ◽

Research Areas ◽

Molecular Neuroscience ◽

The Central Nervous System ◽

To Come ◽

Neuroimaging Genetics ◽

Speech And Language Disorders

Developmental disorders affecting speech and language are highly heritable, but very little is currently understood about the neuromolecular mechanisms that underlie these traits. Integration of data from diverse research areas, including linguistics, neuropsychology, neuroimaging, genetics, molecular neuroscience, developmental biology, and evolutionary anthropology, is becoming essential for unraveling the relevant pathways. Recent studies of the FOXP2 gene provide a case in point. Mutation of FOXP2 causes a rare form of speech and language disorder, and the gene appears to be a crucial regulator of embryonic development for several tissues. Molecular investigations of the central nervous system indicate that the gene may be involved in establishing and maintaining connectivity of corticostriatal and olivocerebellar circuits in mammals. Notably, it has been shown that FOXP2 was subject to positive selection in recent human evolution. Consideration of findings from multiple levels of analysis demonstrates that FOXP2 cannot be characterized as “the gene for speech,” but rather as one critical piece of a complex puzzle. This story gives a flavor of what is to come in this field and indicates that anyone expecting simple explanations of etiology or evolution should be prepared for some intriguing surprises.

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Time-to-event estimation of birth year prevalence trends: a method to enable investigating the etiology of childhood disorders including autism

10.1101/2020.08.05.20169151 ◽

2020 ◽

Author(s):

Alexander MacInnis

Keyword(s):

Diagnostic Criteria ◽

Developmental Disorders ◽

General Purpose ◽

Time To Event ◽

Childhood Disorders ◽

Congenital Diseases ◽

Birth Prevalence ◽

Prevalence Estimation ◽

Age Of Diagnosis ◽

Novel Method

Measures of incidence are essential for investigating etiology. For congenital diseases and disorders of early childhood, birth year cohort prevalence serves the purpose of incidence. There is uncertainty and controversy regarding the birth prevalence trend of childhood disorders such as autism and intellectual disability because changing diagnostic factors can affect the rate and timing of diagnosis and confound the true prevalence trend. The etiology of many developmental disorders is unknown, and it is important to investigate. This paper presents a novel method, Time-to-Event Prevalence Estimation (TTEPE), to accurately estimate the time trend in birth prevalence of childhood disorders correctly adjusted for changing diagnostic factors. There is no known existing method that meets this need. TTEPE is based on established time-to-event (survival) analysis techniques. Input data are rates of initial diagnosis for each birth year cohort by age or, equivalently, diagnostic year. Diagnostic factors form diagnostic pressure, i.e., the probability of diagnosing cases, which is a function of diagnostic year. Changes in diagnostic criteria may also change the effective prevalence at known times. A discrete survival model predicts the rate of initial diagnoses as a function of birth year, diagnostic year, and age. Diagnosable symptoms may develop with age, affecting the age of diagnosis, so TTEPE incorporates eligibility for diagnosis. Parameter estimation forms a non-linear regression using general-purpose optimization software. A simulation study validates the method and shows that it produces accurate estimates of the parameters describing the trends in birth prevalence and diagnostic pressure. The paper states the assumptions underlying the analysis and explores optional additional analyses and potential deviations from assumptions. TTEPE is a robust method for estimating trends in true case birth prevalence controlled for diagnostic factors and changes in diagnostic criteria under certain specified assumptions.

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A Possible Link Between Pyriproxyfen and Microcephaly

10.1101/115279 ◽

2017 ◽

Cited By ~ 2

Author(s):

Yaneer Bar-Yam ◽

H. Frederik Nijhout ◽

Raphael Parens ◽

Felipe Costa ◽

Alfredo J. Morales

Keyword(s):

Juvenile Hormone ◽

Developmental Disorders ◽

Molecular Mechanisms ◽

Viral Infections ◽

Developmental Toxicity ◽

Causal Link ◽

Cross Reactivity ◽

Retinoid X Receptor ◽

Juvenile Hormone Analog ◽

Hormone Analog

The Zika virus has been the primary suspect in the large increase in incidence of microcephaly in 2015-6 in Brazil. However its role is not confirmed despite individual cases in which viral infections were found in neural tissue. Recently, the disparity between the incidences in different geographic locations has led to questions about the virus’s role. Here we consider the alternative possibility that the use of the insecticide pyriproxyfen for control of mosquito populations in Brazilian drinking water is the primary cause. Pyriproxifen is a juvenile hormone analog which has been shown to correspond in mammals to a number of fat soluble regulatory molecules including retinoic acid, a metabolite of vitamin A, with which it has cross-reactivity and whose application during development has been shown to cause microcephaly. Methoprene, another juvenile hormone analog that was approved as an insecticide based upon tests performed in the 1970s, has metabolites that bind to the mammalian retinoid X receptor, and has been shown to cause developmental disorders in mammals. Isotretinoin is another example of a retinoid causing microcephaly in human babies via maternal exposure and activation of the retinoid X receptor in developing fetuses. Moreover, tests of pyriproxyfen by the manufacturer, Sumitomo, widely quoted as giving no evidence for developmental toxicity, actually found some evidence for such an effect, including low brain mass and arhinencephaly—incomplete formation of the anterior cerebral hemispheres—in exposed rat pups. Finally, the pyriproxyfen use in Brazil is unprecedented— it has never before been applied to a water supply on such a scale. Claims that it is not being used in Recife, the epicenter of microcephaly cases, do not distinguish the metropolitan area of Recife, where it is widely used, and the municipality, and have not been adequately confirmed. Given this combination of information about molecular mechanisms and toxicological evidence, we strongly recommend that the use of pyriproxyfen in Brazil be suspended until the potential causal link to microcephaly is investigated further.

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Letters to the Editor

PEDIATRICS ◽

10.1542/peds.40.3.472a ◽

1967 ◽

Vol 40 (3) ◽

pp. 472-473

Author(s):

LEON EISENBERG

Keyword(s):

Kidney Disease ◽

Sodium Transport ◽

Developmental Disorders ◽

Molecular Mechanisms ◽

Letters To The Editor ◽

New Knowledge

I seem not to have made my meaning plain. The pediatrician does not deny responsibility for patients with kidney disease because the molecular mechanisms for renal sodium transport are still in dispute; neither should he disdain developmental disorders because theorists quarrel. In both instances, the good physician undertakes to seek a working synthesis of available evidence even as he and his colleagues search for new knowledge. It was this that I had intended to stress.

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FGF signalling in prostate development, tissue homoeostasis and tumorigenesis

Bioscience Reports ◽

10.1042/bsr20100020 ◽

2010 ◽

Vol 30 (5) ◽

pp. 285-291 ◽

Cited By ~ 16

Author(s):

Yongshun Lin ◽

Fen Wang

Keyword(s):

Tyrosine Kinases ◽

Developmental Disorders ◽

Molecular Mechanisms ◽

Biological Activities ◽

Loss Of Function ◽

Paracrine Factors ◽

Fgf Receptor ◽

Prostate Development ◽

Prostate Carcinogenesis ◽

Fgf Signalling

The FGFs (fibroblast growth factors) regulate a broad spectrum of biological activities by activating transmembrane FGFR (FGF receptor) tyrosine kinases and their coupled intracellular signalling pathways. In the prostate, the mesenchymal–epithelial interactions mediated by androgen signalling and paracrine factors are essential for gland organogenesis, homoeostasis and tumorigenesis. FGFs mediate these mesenchymal–epithelial interactions in the prostate by paracrinal crosstalk through a diverse set of ligands and receptors. Gain- and loss-of-function studies in mouse models have demonstrated the requirement for the FGF signalling axis in prostate development and homoeostasis. The aberrant induction of this axis in either compartment of the prostate results in developmental disorders, disrupts the homoeostatic balance and leads to prostate carcinogenesis. FGFs are also implicated in mediating androgen signalling in the prostate between mesenchymal and epithelial compartments. Therefore studying FGF signalling in the prostate will help us to better understand the underlying molecular mechanisms by which the gland develops, maintains homoeostasis and undergoes carcinogenesis; as well as yield clues on how androgens mediate these processes and how advanced-tumour prostate cells escape strict androgen regulations.

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