Seroprevalence of Hepatitis B virus infection among an afro-descendant community in Brazil

Furnas dos Dionísios is an Afro-Brazilian black community whose descendants were mainly fugitive slaves that established themselves in the State of Mato Grosso do Sul (MS), Brazil. The population is comprised mainly of low socioeconomic individuals who are engaged in agricultural activities. The objective of this study was to investigate the prevalence of hepatitis B (HB) and its correlation with epidemiological data obtained from the community. The studied population totaled 260 individuals with ages varying from 1 to 79 years (median 20). One hundred thirty-three (51.2%) were females and 127 (48.8%) were males. A high prevalence for anti-HBc was observed (42.7%), with present infection detected in 9.2% of the subjects who were also HB surface antigens (HBs Ag) positive; 27.3% were anti-HBc and anti-HBs reactive, and 6.2% had anti-HBc as only marker. The prevalence for anti-HBc was proportional to age, reaching its highest peak in age categories greater than 50. No serological marker was detected in children under the age of 2 years, however anti-HBc was present in 12 subjects with ages between 2 and 14 years, of these 8 (7.4%) were HBsAg positive. Among individuals over the age of 15 years, 99 were anti-HBc reactive, of these 16 (10.5%) were also HBsAg positive, thus suggesting an increased prevalence of HBV carriers among children and adolescents. The risk factors observed in this community that were significantly associated with anti-HBc positivity were age (over 20 years) and having an anti-HBc positive mother. Both HBeAg and anti-HBe were detected in 44.4% of the samples tested. HBsAg subtypes found in the studied population were adw2 (77.7%) and ayw2 (23.3%). While intrafamilial transmission was most likely responsible for HBV infection among children, other routes such as sexual contact might be considered for individuals with ages over 15 years.

Germline mutations in retinoma patients: relevance to low-penetrance and low-expressivity molecular basis.

PURPOSE: To study phenotype-genotype correlation in patients who have retinoma, which is a benign tumor resembling the post irradiation regression pattern of retinoblastoma (RB). METHODS: We selected patients who had retinoma and positive family history for RB and patients who had retinoma in one eye and either retinoma or RB in the other eye. The study included 22 patients with available DNA: 18 from 11 families and four sporadic cases. DNA was extracted from peripheral blood leukocytes. The RB1 gene was screened by DHPLC and direct sequencing of the promoter and all the exons. RESULTS: We identified 17 occurrences of 11 distinct germline mutations in two sporadic and in 15 familial cases (nine families). The 11 identified mutations were located in exons 1, 10,11,13,14, and 19 to 23. Four of the identified mutations were not previously reported, including g.64407delT, g.153236A>T, g.156743delTCTG, and g.162078delA. Eight out the 11 mutations were truncating and three were nontruncating (missense). There was no correlation between the type of mutation and the number of tumor foci per eye (RB or retinomas). Highly heterogeneous intrafamilial expressivity was observed. CONCLUSIONS: To our knowledge, this study is the largest series of mutations of consecutive retinoma patients. The present data suggest that the type of inherited mutations underlying retinoma is undistinguishable from RB related ones, i.e., largely dominated by truncating mutants. This finding is in contrast with the RB1 genotypic spectrum of mutations associated with low-penetrance RB, i.e., nontruncating mutants. The molecular mechanism underlying low-penetrance and attenuated expressivity (retinomas) appeared to be distinct.

Investigation of memory, executive functions, and anatomic correlates in asymptomatic FMR1 premutation carriers.

Fragile X-associated tremor/ataxia syndrome (FXTAS) is a late-onset movement disorder associated with FMR1 premutation alleles. Asymptomatic premutation (aPM) carriers have preserved cognitive functions, but they present subtle executive deficits. Current efforts are focusing on the identification of specific cognitive markers that can detect aPM carriers at higher risk of developing FXTAS. This study aims at evaluating verbal memory and executive functions as early markers of disease progression while exploring associated brain structure changes using diffusion tensor imaging. We assessed 30 aPM men and 38 intrafamilial controls. The groups perform similarly in the executive domain except for decreased performance in motor planning in aPM carriers. In the memory domain, aPM carriers present a significant decrease in verbal encoding and retrieval. Retrieval is associated with microstructural changes of the white matter (WM) of the left hippocampal fimbria. Encoding is associated with changes in the WM under the right dorsolateral prefrontal cortex, a region implicated in relational memory encoding. These associations were found in the aPM group only and did not show age-related decline. This may be interpreted as a neurodevelopmental effect of the premutation, and longitudinal studies are required to better understand these mechanisms.

The PROM1 mutation p.R373C causes an autosomal dominant bull's eye maculopathy associated with rod, rod-cone, and macular dystrophy.

PURPOSE: To characterize in detail the phenotype of five unrelated families with autosomal dominant bull's eye maculopathy (BEM) due to the R373C mutation in the PROM1 gene. METHODS: Forty-one individuals of five families of Caribbean (family A), British (families B, D, E), and Italian (family C) origin, segregating the R373C mutation in PROM1, were ascertained. Electrophysiological assessment, fundus autofluorescence (FAF) imaging, fundus fluorescein angiography (FFA), and optical coherence tomography (OCT) were performed in available subjects. Mutation screening of PROM1 was performed. RESULTS: The R373C mutant was present heterozygously in all affected patients. The age at onset was variable and ranged between 9 and 58 years, with most of the individuals presenting with reading difficulties. Subjects commonly had a mild to moderate reduction in visual acuity except for members of family C who experienced markedly reduced central vision. The retinal phenotype was characterized by macular dystrophy, with retinal pigment epithelial mottling in younger subjects, progressing to typical BEM over time, with the development of macular atrophy in older patients. In addition, all members of family C had typical features of RP. The electrophysiological findings were variable both within and between families. CONCLUSIONS: Mutations in PROM1 have been described to cause a severe form of autosomal recessive RP in two families of Indian and Pakistani descent. The results of this study have demonstrated that a distinct redundant PROM1 mutation (R373C) can also produce an autosomal dominant, fully penetrant retinopathy, characterized by BEM with little inter- and intrafamilial variability, and retinal dystrophy with variable rod or rod-cone dysfunction and marked intra- and interfamilial variability, ranging from isolated maculopathy without generalized photoreceptor dysfunction to maculopathy associated with very severe rod-cone dysfunction.

Heritability of the retinal microcirculation in flemish families.

BACKGROUND Few population studies have described the heritability and intrafamilial concordance of the retinal microvessels, or the genetic or environmental correlations of the phenotypes of these vessels. METHODS We randomly selected 413 participants from 70 families (mean age, 51.5 years; 50.1% women) from a Flemish population. We postprocessed retinal images using IVAN software to generate the central retinal arteriole equivalent (CRAE), central retinal venule equivalent (CRVE), and arteriole-to-venule-ratio (AVR) from these images. We used SAGE version 6.2 and SAS version 9.2 to compute multivariate-adjusted estimates of heritability and intrafamilial correlations of the CRAE, CRVE, and AVR of the retinal microvessels in the images. RESULTS Sex, age, mean arterial pressure, and smoking explained up to 12.7% of the variance of the phenotypes of the retinal microvessels of the study participants. With adjustments applied for these covariates, the heritability estimates of CRAE, CRVE, and AVR were 0.213 (P = 0.044), 0.339 (P = 0.010), and 0.272 (P = 0.004), respectively. The parent-offspring correlations for CRAE, CRVE, and AVR were 0.118 (NS), 0.225 (P < 0.01), and 0.215 (P < 0.05), respectively. The corresponding values were 0.222 (P < 0.05), 0.213 (P < 0.05), and 0.390 (P < 0.001) for sib-sib correlations, respectively. The genetic and environmental correlations between CRAE and CRVE were 0.360 and 0.545 (P < 0.001 for both). CONCLUSION Our study showed moderate heritability for CRAE, CRVE, and AVR, and a significant genetic correlation of CRAE with CRVE in the Flemish population of our study. These findings suggest that genetic factors influence the diameter of the retinal microvessels, and that CRAE and CRVE share some genetic determinants.

Defining the Effect of the 16p11.2 Duplication on Cognition, Behavior, and Medical Comorbidities.

IMPORTANCE: The 16p11.2 BP4-BP5 duplication is the copy number variant most frequently associated with autism spectrum disorder (ASD), schizophrenia, and comorbidities such as decreased body mass index (BMI). OBJECTIVES: To characterize the effects of the 16p11.2 duplication on cognitive, behavioral, medical, and anthropometric traits and to understand the specificity of these effects by systematically comparing results in duplication carriers and reciprocal deletion carriers, who are also at risk for ASD. DESIGN, SETTING, AND PARTICIPANTS: This international cohort study of 1006 study participants compared 270 duplication carriers with their 102 intrafamilial control individuals, 390 reciprocal deletion carriers, and 244 deletion controls from European and North American cohorts. Data were collected from August 1, 2010, to May 31, 2015 and analyzed from January 1 to August 14, 2015. Linear mixed models were used to estimate the effect of the duplication and deletion on clinical traits by comparison with noncarrier relatives. MAIN OUTCOMES AND MEASURES: Findings on the Full-Scale IQ (FSIQ), Nonverbal IQ, and Verbal IQ; the presence of ASD or other DSM-IV diagnoses; BMI; head circumference; and medical data. RESULTS: Among the 1006 study participants, the duplication was associated with a mean FSIQ score that was lower by 26.3 points between proband carriers and noncarrier relatives and a lower mean FSIQ score (16.2-11.4 points) in nonproband carriers. The mean overall effect of the deletion was similar (-22.1 points; P < .001). However, broad variation in FSIQ was found, with a 19.4- and 2.0-fold increase in the proportion of FSIQ scores that were very low (≤40) and higher than the mean (>100) compared with the deletion group (P < .001). Parental FSIQ predicted part of this variation (approximately 36.0% in hereditary probands). Although the frequency of ASD was similar in deletion and duplication proband carriers (16.0% and 20.0%, respectively), the FSIQ was significantly lower (by 26.3 points) in the duplication probands with ASD. There also were lower head circumference and BMI measurements among duplication carriers, which is consistent with the findings of previous studies. CONCLUSIONS AND RELEVANCE: The mean effect of the duplication on cognition is similar to that of the reciprocal deletion, but the variance in the duplication is significantly higher, with severe and mild subgroups not observed with the deletion. These results suggest that additional genetic and familial factors contribute to this variability. Additional studies will be necessary to characterize the predictors of cognitive deficits.

Pollen morphology of species of Hortia (Rutaceae)

A palinological study covering all 10 species of the Neotropical genus Hortia Vand. (Rutaceae) was conducted. Pollen grains were collected from herbarium exsiccates, acetolysed and mounted in glycerine jelly on glass slides. The grains were studied under light and scanning electron microscopy, including measurements of polar and equatorial diameters, shape of the grains, number and shape of apertures, and thickness of the exine. The results demonstrated that the genus is stenopalynous, with pollen grains in monads, subprolate to prolate, 3-colporate, with very thick exine and a psilate-perforate pattern of ornamentation. Pollen grains of all species revealed a great similarity, with few variations in the pattern of ornamentation of exine, number and form of apertures and measurements. Although well-characterized palinologycally, pollen features did not furnish relevant information on the position of Hortia into an intrafamilial phylogeny.

Oculo-facio-cardio-dental syndrome in three succeeding generations: genotypic data and phenotypic features

Oculo-facio-cardio-dental (OFCD) syndrome is a rare X-linked disorder mainly manifesting in females. Patients show ocular, facial, cardiac, and dental abnormalities. OFCD syndrome is caused by heterozygous mutations in the BCOR gene, located in Xp11.4, encoding the BCL6 co-repressor. We report a Croatian family with four female members (grandmother, mother and monozygotic female twins) diagnosed with OFCD syndrome who carry the novel BCOR mutation c.4438C>T (p.R1480*). They present high intrafamilial phenotypic variability with special regard to cardiac defect and cataract that showed more severe disease expression in successive generations. Clinical and radiographic examination of the mother of the twins revealed a talon cusp involving the permanent maxillary right central incisor. This is the first known report of a talon cusp in OFCD syndrome with a novel mutation in the BCOR gene.

Identification des indices comportementaux reliés à la présence d'intérêts sexuels déviants chez les agresseurs sexuels d’enfants

Lors de l’élaboration du diagnostic de trouble pédophilique (DSM-5; APA, 2013), un critère basé sur un minimum de victimes avait été proposé pour poser le diagnostic lorsque les agresseurs sexuels d’enfants ne se reconnaissent pas d’attirance sexuelle déviante, et qu’une évaluation pléthysmographique de leurs intérêts sexuels n’est pas disponible ou invalide. Il avait aussi été proposé de créer des sous-types selon le groupe d’âge préféré sexuellement ou l’âge des victimes : pédophilique (victimes prépubères, 10 ans et moins), hébéphilique (victimes en début de puberté, 11-14 ans) ou pédohébéphilique (les deux). Ces propositions ont soulevé la controverse parmi les chercheurs et cliniciens et n’ont pas été acceptées en raison du manque de soutien empirique les appuyant. Cette thèse tente de répondre aux principaux questionnements soulevés : 1) Quels indices comportementaux devraient être utilisés pour évaluer la déviance sexuelle chez les agresseurs sexuels d’enfants intrafamiliaux et extrafamiliaux respectivement? 2) Le nombre d’interactions sexuelles avec un même enfant et la durée de la période des agressions sont-ils reliés à la déviance sexuelle? 3) Les agresseurs sexuels d’enfants en début de puberté présentent-ils des intérêts sexuels déviants? Le premier article est un commentaire sur le DSM-5 présentant les grandes lignes de la thèse et les résultats préliminaires des deux articles suivants. Le deuxième article vise à répondre aux deux premières questions. Des agresseurs sexuels d'enfants intrafamiliaux (n = 76) et extrafamiliaux (n = 93) sont comparés quant au nombre, l’âge et le sexe de leurs victimes, le nombre d’interactions sexuelles avec une même victime et la durée de la période des agressions, et leurs intérêts sexuels autorapportés ou évalués avec la pléthysmographie pénienne. Les relations entre ces indices comportementaux et la présence d'intérêts sexuels déviants sont évaluées pour les deux groupes. Les résultats suggèrent que : 1) différents indices comportementaux devraient être utilisés lors de l’évaluation des intérêts sexuels selon les groupes d’agresseurs; 2) des agressions répétées et de longues durées sur une même victime suggèrent la déviance sexuelle chez les agresseurs intrafamiliaux, alors qu’aucune relation n’est observée entre ces variables chez les agresseurs extrafamiliaux. Cette recherche ii constitue une première étape vers l’utilisation du nombre et de la durée des agressions sexuelles avec un même enfant lors de l’évaluation des intérêts sexuels des agresseurs sexuels d’enfants. Le troisième article vise à répondre à la dernière question énoncée. Des agresseurs sexuels d'enfants regroupés selon l’âge de leurs victimes, pédophilique (n = 75), hébéphilique (n = 44), pédohébéphilique (n = 49), sont comparés quant à différentes variables : nombre et sexe des victimes, historique criminel, et intérêts sexuels autorapportés ou mesurés avec la pléthysmographie. Les résultats montrent la présence d’intérêts sexuels déviants dans les mêmes proportions pour les trois groupes. Quant aux autres variables, les groupes « pédophilique » et « hébéphilique » se distinguent peu, mais ils diffèrent du groupe « pédohébéphilique ». Ces résultats appuient le chevauchement entre l’attirance sexuelle envers les enfants prépubères et l’attirance envers ceux en début de puberté, et soutiennent leur regroupement dans le diagnostic de trouble pédophilique.

Analyse des facteurs biodémographiques, sociéconomiques et familiaux de la longévité exceptionnelle

La recherche des facteurs de longévité gagne en intérêt dans le contexte actuel du vieillissement de la population. De la littérature portant sur la longévité et la mortalité aux grands âges, un constat émerge : bien que les déterminants associés à la survie humaine soient multiples, l'environnement familial aurait un rôle déterminant sur la mortalité et sur l'atteinte des âges avancés. Dès lors, l'objectif de cette thèse est d'évaluer les déterminants de la survie exceptionnelle et d'examiner le rôle des aspects familiaux, en début de vie et à l'âge adulte, dans les différentiels de durée de vie. Plus spécifiquement, elle vise à : (1) examiner la similarité des âges au décès entre frères, soeurs et conjoints afin d'apprécier l'ampleur de la composante familiale de la longévité; (2) explorer, d'un point de vue intrafamilial, les conséquences à long terme sur la survie des variables non partagées issues de la petite enfance tels l'âge maternel à la reproduction, le rang de naissance et la saison de naissance; et (3) s'interroger sur le rôle protecteur ou délétère de l’environnement et du milieu familial d'origine dans l’enfance sur l'atteinte des grands âges et dans quelle mesure le statut socioéconomique parvient à médiatiser la relation. Cette analyse s'appuie sur le jumelage des recensements canadiens et des actes de décès de l’état civil québécois et emploie des données québécoises du 20e siècle issues de deux échantillons distincts : un échantillon aléatoire représentatif de la population provenant du recensement canadien de 1901 ainsi qu’un échantillon de frères et soeurs de centenaires québécois appartenant à la même cohorte. Les résultats, présentés sous forme d'articles scientifiques, ont montré, en outre, que les frères et soeurs de centenaires vivent plus longtemps que les individus appartenant aux mêmes cohortes de naissance, reflétant la contribution d'une robustesse commune, mais également celle de l'environnement partagé durant la petite enfance. Ces analyses ont également témoigné d'un avantage de survie des conjoints des centenaires, soulignant l'importance d'un même environnement à l'âge adulte (1er article). De plus, nos travaux ont mis de l'avant la contribution aux inégalités de longévité des variables biodémographiques issues de l'environnement non partagé telles que l'âge maternel à la reproduction, le rang de naissance et la saison de naissance, qui agissent et interagissent entre elles pour créer des vulnérabilités et influer sur l'atteinte des âges exceptionnels (2e article). Enfin, une approche longitudinale a permis de souligner la contribution du milieu social d'origine sur la longévité, alors que les individus issus d’un milieu socioéconomique défavorisé pour l'époque (milieu urbain, père ouvrier) vivent moins longtemps que ceux ayant vécu dans un environnement socioéconomique favorable (milieu rural, fermier), résultat d'une potentielle accumulation des avantages liée à la reproduction du statut social ou d'une programmation précoce des trajectoires de santé. L’influence est toutefois moindre pour les femmes et pour les frères de centenaires et s'exprime, dans ce cas, en partie par l'effet de la profession à l'âge adulte (3e article).

Disturbances in morning cortisol secretion in association with maternal postnatal depression predict subsequent depressive symptomatology in adolescents

Background: We have previously reported higher and more variable salivary morning cortisol in 13-year-old adolescents whose mothers were depressed in the postnatal period, compared with control group adolescents whose mothers did not develop postnatal depression (PND). This observation suggested a biological mechanism by which intrafamilial risk for depressive disorder may be transmitted. In the current article, we examined whether the cortisol disturbances observed at 13 years could predict depressive symptornatology in adolescents at 16 years of age. Methods: We measured self-reported depressive symptoms in 16-year-old adolescents who had (n = 48) or had not (n = 39) been exposed to postnatal maternal depression and examined their prediction by morning and evening cortisol indices obtained via 10 days of salivary collections at 13 years. Results: Elevated morning cortisol secretion at 13 years, and particularly the maximum level recorded over 10 days of collection, predicted elevated depressive symptoms at 16 years over and above 13-year depressive symptom levels and other possible confounding factors. Morning cortisol secretion mediated an association between maternal PND and symptornatology in 16-year-old offspring. Conclusions: Alterations in steroid secretion observed in association with maternal PND may provide a mechanism by which risk for depression is transmitted from mother to offspring.

Oculoauriculovertebral spectrum: report of nine familial cases with evidence of autosomal dominant inheritance and review of the literature

Oculoauriculovertebral spectrum (OAVS; OMIM 164210) is a complex condition characterized by defects of aural, oral, mandibular and vertebral development. The aetiology of this condition is likely to be heterogeneous; most cases are sporadic, however, familial cases suggesting autosomal recessive end autosomal dominant inheritance have been reported. In this study, we describe the clinical aspects of nine familial cases with evidence of autosomal dominant inheritance and compare them with reports in the literature. Interfamilial and intrafamilial clinical variabilities were observed in this study (reinforcing the necessity of careful examination of familial members). We suggest that oculoauriculovertebral spectrum with autosomal dominant inheritance is characterized mainly by bilateral auricular involvement and rarely presents extracranial anomalies. Clin Dysmorphol 18:67-77 (C) 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins.

Transcriptional regulation differs in affected facioscapulohumeral muscular dystrophy patients compared to asymptomatic related carriers

Facioscapulohumeral muscular dystrophy (FSHD) is a progressive muscle disorder that has been associated with a contraction of 3.3-kb repeats on chromosome 4q35. FSHD is characterized by a wide clinical inter- and intrafamilial variability, ranging from wheelchair-bound patients to asymptomatic carriers. Our study is unique in comparing the gene expression profiles from related affected, asymptomatic carrier, and control individuals. Our results suggest that the expression of genes on chromosome 4q is altered in affected and asymptomatic individuals. Remarkably, the changes seen in asymptomatic samples are largely in products of genes encoding several chemokines, whereas the changes seen in affected samples are largely in genes governing the synthesis of GPI-linked proteins and histone acetylation. Besides this, the affected patient and related asymptomatic carrier share the 4qA161 haplotype. Thus, these polymorphisms by themselves do not explain the pathogenicity of the contracted allele. Interestingly, our results also suggest that the miRNAs might mediate the regulatory network in FSHD. Together, our results support the previous evidence that FSHD may be caused by transcriptional dysregulation of multiple genes, in cis and in trans, and suggest some factors potentially important for FSHD pathogenesis. The study of the gene expression profiles from asymptomatic carriers and related affected patients is a unique approach to try to enhance our understanding of the missing link between the contraction in D4Z4 repeats and muscle disease, while minimizing the effects of differences resulting from genetic background.

Chemotaxonomic relationships in Celastraceae inferred from principal component analysis (PCA) and partial least squares (PLS)

This paper describes a chemotaxonomic analysis of a database of triterpenoid compounds from the Celastraceae family using principal component analysis (PCA). The numbers of occurrences of thirty types of triterpene skeleton in different tribes of the family were used as variables. The study shows that PCA applied to chemical data can contribute to an intrafamilial classification of Celastraceae, once some questionable taxa affinity was observed, from chemotaxonomic inferences about genera and they are in agreement with the phylogeny previously proposed. The inclusion of Hippocrateaceae within Celastraceae is supported by the triterpene chemistry.

Genetic polymorphism of Streptococcus mutans in Brazilian family members

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)