Developmental absence of maxillary lateral incisors in the Portuguese population

The aim of this study was to evaluate the prevalence and clinical manifestation of developmental absence of maxillary permanent lateral incisors in the Portuguese population. The study group comprised 16 771 patients observed between 1993 and 2000 at the Faculty clinic. Two hundred and nineteen patients were found to have missing upper lateral incisors (131 females and 88 males, with ages ranging between 3 and 71 years), a prevalence of 1.3 per cent in this population. Absence of these teeth was bilateral in 44.7 per cent of the patients; of the unilateral cases, 33 per cent occurred on the right side and 21.9 per cent on the left side. In children under 8 years of age (n = 12), two (0.26 per cent) also had developmental absence of the primary lateral incisors, one unilateral and the other bilateral. Among the 121 subjects with unilateral developmental absence, the contralateral maxillary lateral incisor was found to be microdont in 57.1 per cent (right lateral 23 per cent, left lateral 34.1 per cent), suggesting the possibility that microdontia represents a variable expression of the same developmental defect that results in absence

Different manifestations of Class II Division 2 incisor retroclination – Morphologic study

NOTICE: this is the author’s version of a work that was accepted for publication in American Journal of Orthodontics and Dentofacial Orthopedics. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in American Journal of Orthodontics and Dentofacial Orthopedics, [Vol. 143, Issue 3, (March 2013)] DOI 10.1016/j.ajodo.2012.09.021."Introduction: The aim of the present study was to investigate whether there is a different transverse morphologic pattern of dental arches among the different manifestations of Class II Division 2 incisor retroclination and evaluate to what extent the pattern of smaller-than-average teeth in Class II Division 2 malocclusion is common to all groups studied. This information may clarify whether different Class II Division 2 phenotypes represent a single etiology or multiple etiologies. Methods: The sample comprised 108 Class II Division 2 malocclusions which were divided into two groups according to the type of incisor retroclination: Group I composed of 43 Class II Division 2 with retroclination exclusively of the maxillary central incisors; Group II composed of 65 Class II Division 2 with retroclination of the four maxillary incisors. Maxillary and mandibular intercanine and intermolar widths as well as the mesiodistal crown dimension of the four maxillary and mandibular incisors were determined using the initial study models of patients. Mean values of all variables were compared between the two groups by gender using ANOVA. Results: From the comparison between the two groups analyzed, no statistically significant differences were found for all transverse measurements (p>0.05). For all mesiodistal measurements analyzed, statistically significant differences between the groups were only found for the mean value of both maxillary lateral incisors mesiodistal dimension in both sexes (p<0.05). Conclusions: It is not possible to attribute a characteristic pattern of dental arch width and of incisor mesiodistal dimension to the different manifestations of incisor retroclination in Class II Division 2 malocclusion.

Different manifestations of class II division 2 incisor retroclination and their association with dental anomalies

Notice: this is the author’s version of a work that was accepted for publication in Journal of Orthodontics. Changes resulting from the publishing process may not be reflected in this document. Final version available in Journal of Orthodontics. Vol. 40, Issue 4, (December 2013). DOI 10.1179/1465313313Y.0000000067."Objective: To investigate whether there is an association between dental development anomalies (DDAs) and the different manifestations of Class II Division 2 (CII/2) malocclusion incisor retroclination. This information may clarify whether the different CII/2 phenotypes, with regard to maxillary incisor retroclination, are a single clinical entity or etiologically different entities. Design: Retrospective comparative study. Setting: Private orthodontic practice in the regions of Lisbon and Porto, Portugal Subjects and Methods: The sample comprised 115 CII/2 malocclusions distributed into 2 groups on the basis of incisor retroclination: Group I composed of 48 CII/2 with retroclination exclusively of both maxillary central incisors; Group II composed of 67 CII/2 with retroclination of all four maxillary incisors. Using the initial orthodontic records, it was determined for each patient the presence of the following DDAs: tooth impaction, tooth agenesis, maxillary lateral incisor microdontia, tooth transpositions and supernumerary teeth. Results: 55.0% of patients were diagnosed with at least one of the DDAs studied. In the total sample the prevalence rates were determined as follows: 20.0% of palatal maxillary canine impaction, 27.4% of third molar agenesis, and 15.7% of maxillary lateral incisor microdontia. No patient exhibited any transpositions or supernumerary teeth. The distribution of the DDAs studied by groups revealed a strong association of palatal canine impaction, tooth agenesis and maxillary lateral incisor microdontia with Groups II but not with Group I. Conclusion: The association of DDAs with CII/2 malocclusion is not common to all types of maxillary incisor retroclination, suggesting different etiologic bases among the different manifestations of CII/2 malocclusion incisor retroclination.

Instability of mRNA expression signatures of drug transporters in chronic myeloid leukemia patients resistant to imatinib

Despite the success of imatinib mesylate (IM) in the treatment of chronic myeloid leukemia (CML), approximately 30\% of patients are resistant to therapy, mostly due to unknown causes. To profile the expression signatures of drug transporters throughout IM therapy and correlate them with resistance, we quantified mRNA expression levels of the SLC22A12, ABCB1, ABCC1, ABCG2 and MVP genes in consecutive samples from peripheral blood or bone marrow of CML patients who were either responsive or resistant to IM. Additionally we identified and quantified BCR-ABL1 transcript variants and analyzed 1236T>C ABCB1 and 480G>C SLC22A1 polymorphisms. A relationship between the type of BCR-ABL1 transcript or ABCB1 or SLC22A1 genotype and response to treatment was not discovered. However, the studied genes had higher expression levels in follow-up compared to the diagnostic samples, demonstrating a possible induction in expression. IM-sensitive patients presented significantly higher values of SLC22A1 expression, suggesting higher drug influx. Most importantly, while responding patients demonstrated stable expression signatures in consecutive samples, there was considerable variation in IM-resistant patients, indicating that single point sampling expression signatures are not reliable in predicting clinical outcomes or prognostic features in these patients. Studies that assessed consecutive samples from CML patients in order to evaluate the variation in expression levels of transporter genes are limited yet our study emphasizes the importance of such approaches.publishersversionpublishe

PROTOPORFIRIA ERITROPOIÉTICA – Caracterização de uma Família Portadora de uma Nova Mutação no Gene FECH

Erythropoietic protoporphyria (EPP) is a rare inherited disorder of heme biosynthesis caused in most patients by a deficient activity of the enzyme ferrochelatase (FECH), with a consequent accumulation of protoporphyrin (PP) in various tissues. We report a 16-year-old male (index case) with EPP characterized by acute episodes of painful photosensitivity in the photoexposed areas since his early infancy, permanent changes, microcytic anemia, thrombocytopenia and mild hepatic dysfunction. His 18-year-old sister presented slighter acute symptoms and had no chronic changes. Lesional biopsy performed in index case disclosed perivascular deposition of PAS positive hyaline material. Rimington-Cripps test was positive in both cases and PP erythrocyte levels were markedly elevated, but normal in their asymptomatic parents and younger brother. Genetic study in both patients and their mother (father’s sample not available) revealed heterozygosity for a novel mutation (c.1052delA) in FECH gene of both children, and heterozygosity for the hypomorphic allele IVS3-48T&gt;C in all of them. This report confirms the “pseudodominant” inheritance pattern observed in most studied families, explained by the combined presence of a disabling FECH mutation and a common intronic polymorphism affecting the counterpart allele (IVS3-48T&gt;C). The mutant allele was probably inherited from the father. This is the first description of a Portuguese family with EPP characterized at the molecular level.A protoporfiria eritropoiética (PPE), é uma genodermatose rara causada, na maioria dos doentes, pela redução da actividade da ferroquelatase (FECH), a última enzima da biossíntese do heme, e consequente acumulação de protoporfirina (PP) em vários tecidos. Os autores descrevem um adolescente de 16 anos (caso índice) que sofria de PPE desde a infância, caracterizada por episódios agudos de fotossensibilidade dolorosa nas áreas foto-expostas, alterações crónicas, anemia microcítica, trombocitopenia e disfunção hepática ligeira. A irmã de 18 anos apresentava sintomas agudos mais ligeiros e não evidenciava alterações crónicas. Os progenitores e o irmão mais novo eram assintomáticos. A biópsia lesional efectuada no caso índice mostrou deposição de material hialino, PAS-positivo, em localização perivascular. O teste de Rimington-Cripps foi positivo em ambos os doentes sintomáticos e os níveis de PPs eritrocitárias encontravam-se elevados, mas normais nos pais e no irmão mais novo. O estudo genético, efectuado em ambos os doentes e na mãe (amostra do pai não disponível por paradeiro desconhecido), revelou heterozigotia para uma nova mutação no gene FECH (c.1052delA) nos filhos e heterozigotia para o alelo hipomórfico IVS3-48T&gt;C em todos os elementos testados. Confirmou-se, assim, o padrão de hereditariedade “pseudodominante” observado na maioria das famílias, explicado pela presença simultânea de uma mutação no gene FECH e de um polimorfismo frequente, afectando o alelo oposto (IVS3-48T&gt;C). Neste caso, o alelo mutante foi provavelmente herdado do pai. Do nosso conhecimento, esta é a primeira descrição de uma família portuguesa com PPE caracterizada do ponto de vista molecular, tendo-se descrito uma nova mutação, não referida na literatura

The contribution of 7q33 copy number variations for intellectual disability

Copy number variations (CNVs) at the 7q33 cytoband are very rarely described in the literature, and almost all of the cases comprise large deletions affecting more than just the q33 segment. We report seven patients (two families with two siblings and their affected mother and one unrelated patient) with neurodevelopmental delay associated with CNVs in 7q33 alone. All the patients presented mild to moderate intellectual disability (ID), dysmorphic features, and a behavioral phenotype characterized by aggressiveness and disinhibition. One family presents a small duplication in cis affecting CALD1 and AGBL3 genes, while the other four patients carry two larger deletions encompassing EXOC4, CALD1, AGBL3, and CNOT4. This work helps to refine the phenotype and narrow the minimal critical region involved in 7q33 CNVs. Comparison with similar cases and functional studies should help us clarify the relevance of the deleted genes for ID and behavioral alterations.FEDER funds, through the Competitiveness Factors Operational Programme (COMPETE), and by National funds, through the Foundation for Science and Technology (FCT), under the scope of the projects PIC/IC/83026/2007, PIC/IC/83013/2007, and POCI-01-0145-FEDER-007038. This work has also been funded by the project NORTE-01-0145-FEDER-000013, supported by the Northern Portugal Regional Operational Programme (NORTE 2020), under the Portugal 2020 Partnership Agreement, through the European Regional Development Fund (FEDER)info:eu-repo/semantics/publishedVersio

Root Resorption in Orthodontics - Genetic Susceptibility?

OBJECTIVES: External root resorption (ERR) is a condition that can be observed in association with orthodontic treatment. The etiology of root resorption is complex, related with several factors. Some inflammatory mediators, controlled by specific genes, have been associated with bone resorption and in the recruitment of osteoclasts during orthodontic movement (Lee et al., 2007; Abass et al., 2008; Bastos et al., 2009). Particularly the association between polymorphisms in the IL-1B gene and ERR during orthodontic treatment has been referenced in literature. The present paper as the principal objective to present a case of an orthodontic patient, Caucasian, gender male, 15 years old, with positive family history of generalized ERR associated to orthodontic treatment (one sister), and there was therefore need to clarify the role of genetic susceptibility in its pathogenesis. MATERIALS AND METHODS: It was performed a literature review on PUBMED with the key words dental orthodontics resorption genetics, 12 articles were obtained and were included 8 of these. There were also associated with the theme 7 more articles, from the list of related articles. The search was limited to the last 10 years and the English, French and Spanish. RESULTS: As there was positive family history of the ERR was decided to perform a genetic test for determination of single polymorphisms for IL1B gene (TGP, CGC Clinical Genetics Center, Portugal), which revealed the presence of an allele of the IL1B gene - positive result for ERR. The absence of external etiological factors associated with orthodontic treatment was suggestive of possible individual genetic susceptibility. CONCLUSIONS: The identification of individuals with increased susceptibility to ERR should be considered during the orthodontic treatment plan, to allow adjustments necessary in terms of magnitude of the force to be applied, both in terms of duration of treatment

Sequências de tempos em completivas finitas: restrições lexicais e efeitos na aquisição

This paper is focused on the distribution of tenses in finite complement clauses in Portuguese. We first show that the concept of tense dependence does not explain all the restrictions to tenses in embedded clauses. Both temporal orientation and other semantic factors constrain the tenses that may occur in a complement clause. We also analyse tense sequences in a corpus of child spontaneous speech. In light of our previous analysis, we suggest an early restriction in child grammar: the sequences of tenses produced by the child in first stages may suggest avoidance of tense dependence