Inheritance pattern of molar-incisor hypomineralization

Abstract The aim of this study was to investigate the segregation patterns of molar incisor hypomineralization (MIH) in families, given the evidence that its etiology is influenced by genetics. Clinically, MIH may be detected in parents and/or siblings of MIH-affected children. Our study included children with at least one first permanent molar affected by MIH (proband) and their first-degree relatives (parents and siblings). The participants were examined clinically to detect MIH, according to the European Academy of Paediatric Dentistry criteria (2003). A total of 101 nuclear families (391 individuals) were studied. Proband diagnosis was followed by MIH classification of the subject, his parents and siblings, as affected, unaffected, or unknown. Segregation analysis was performed using the multivariate logistic regression model of the Statistical Analysis for Genetic Epidemiology package, and segregation models (general transmission, environmental, major gene, dominant, codominant and recessive models). The Akaike information criterion (AIC) was used to evaluate the most parsimonious model. In all, 130 affected individuals, 165 unaffected individuals, and 96 unknown individuals were studied. Severe MIH was found in 50.7% of the cases. A segregation analysis performed for MIH revealed the following different models: environmental and dominance (p = 0.05), major gene (p = 0.04), codominant (p = 0.15) and recessive models (p = 0.03). According to the AIC values, the codominant model was the most parsimonious (AIC = 308.36). Our results suggest that the codominant model could be the most likely for inheriting MIH. This result strengthens the evidence that genetic factors, such as multifactorial complex defect, influence MIH.

Análise Temporal dos Transcritos dos Genes bdnf e ntrk2 em Cérebro de Zebrafish Induzido à Crise Epiléptica por Pentilenotetrazol / Temporal transcript profile of bdnf, ntrk2a and ntrk2b genes in zebrafish brain after Pentylenotetrazole (PTZ)-induced seizure

Objetivo: Investigar o perfil temporal de transcritos dos genes bdnf, ntrk2a e ntrk2b em cérebro de zebrafish após crise epiléptica induzida por Pentilenotetrazol (PTZ). Metodologia: Os animais foram divididos em Grupo PTZ (induzidos à crise epiléptica com PTZ 15mM) e Grupo Controle (animais sem crise epiléptica) e seus cérebros coletados nos tempos: 0h, 12h, 24h, 48h, 72h pós-crise. Reações de transcriptase reversa-PCR quantitativa foram realizadas com os controles endógenos 18s e ef1a usando-se o sistema TaqManTM (Applied Biosystems, Foster City). A quantificação relativa foi calculada pela equação QR=2–∆∆CT e a significância estatística dada pelo teste Kruskall-Wallis (p≤0,05). Resultados: No grupo PTZ houve um aumento significativo dos niveis de RNAm do gene bdnf no tempo 0h (p=0,017). O aumento de transcritos encontrado nos outros tempos não foi significante (p>0,05). Conclusão: Nossos resultados mostraram que a indução de crise epiléptica alterou o padrão de transcrito do gene bdnf no cérebro do zebrafish como visto em outros modelos animais e em humanos, porém em um padrão temporal diferente. Este é o primeiro estudo que descreve o perfil temporal de transcritos bdnf/ntrk2 em cérebro de zebrafish após crise epiléptica e contribui para a caracterização deste pequeno peixe como modelo de estudo em epilepsias.

Objective: The main aim of this study was to investigate the transcript profile of bdnf, ntrk2a and ntrk2b genes in adult zebrafish brain after Pentylenotetrazole (PTZ)-induced seizure. Methods: Zebrafish were separated in PTZ (seizure-induced) and Control (no seizure) groups. At 0h, 12h, 24h, 48h and 72h after seizure, animals were anesthetized and their brains were immediately collected for RNA extraction. Reverse transcriptase quantitativePCRs were carried out with 18S and ef1a as endogenous control using TaqManTM System (Applied Biosystems, Foster City). The relative quantification was calculated by the equation RQ=2–∆∆CT. Statistical analysis was performed by Kruskall-Wallis test (p≤0.05). Results: Comparisons between both groups showed an increase of bdnf mRNA levels in the PTZ group at 0h after seizure (p= 0.017). No statistical significance was found in other times investigated (p>0.05). Conclusions: Our results showed an up-regulation of the transcript levels of bdnf gene in zebrafish brain after seizure as seems in other models and humans, but in a different pattern. This is the first study investigating temporal pattern of bdnf, ntrk2a and ntrk2b genes in zebrafish brain after a seizure and contributes to characterize it as a model for epilepsy studies.

Linkage study of voltage-gated potassium channels in familial mesial temporal lobe epilepsy

Voltage-gated potassium channels (VGKCs) play a critical role in the regulation of neuronal excitability and have been implicated in some types of epilepsies. Recently, autoimmune limbic encephalitis (LE) was associated with antibodies against VGKC. In addition, patients with LE showed partial epilepsy and increased T2 signal abnormalities in limbic structures. We have reported familial mesial temporal lobe epilepsy (FMTLE) associated with hippocampal atrophy (HA) and other signs of mesial temporal sclerosis detected by magnetic resonance imaging (MRI). In order to investigate whether VGKC may be associated to HA present in FMTLE, we perform linkage study in these candidate genes. Seventy-three microsatellites markers were genotyped in different human autosomal chromosome. Two-point LOD scores did not show evidence for linkage with any of the microsatellite markers genotyped (Zmax ranging from 0.11to-9.53 at theta=0.00). In the present study, linkage data showed no evidence that VGKC are involved in the determination of HA in FMTLE.

Canais de potássio voltagem-dependentes (CPVD) desempenham importante papel na excitabilidade neuronal e estão associados a determinados tipos de epilepsia. Recentemente, um tipo de encefalite límbica autoimune (EL) foi associado com anticorpos contra CPVD. Além disso, há relatos de pacientes com EL e epilepsia parcial, além de hipersinal em regiões límbicas detectadas em imagens de ressonância magnética (IRM). Nós temos descrito a epilepsia de lobo temporal mesial familial (ELTMF) associada à atrofia hipocampal (AH) e outros sinais de esclerose mesial temporal observadas em IRM. Para investigar se os CPVD podem estar associados com a AH identificada na ELTMF, empregamos o estudo de ligação genética nesses genes candidatos. Setenta e três marcadores microssatélites foram genotipados e o LOD score de dois pontos mostrou Zmax variando de 0.11 a -9.53 para teta=0.00. No presente estudo, os dados obtidos com a análise de ligação mostram que os CPVD não estão envolvidos na determinação da AH na ELTMF.