Epidemiological Surveillance of Birth Defects Compatible with Thalidomide Embryopathy in Brazil

The thalidomide tragedy of the 1960s resulted in thousands of children being born with severe limb reduction defects (LRD), among other malformations. In Brazil, there are still babies born with thalidomide embryopathy (TE) because of leprosy prevalence, availability of thalidomide, and deficiencies in the control of drug dispensation. Our objective was to implement a system of proactive surveillance to identify birth defects compatible with TE. Along one year, newborns with LRD were assessed in the Brazilian hospitals participating in the Latin-American Collaborative Study of Congenital Malformations (ECLAMC). A phenotype of LRD called thalidomide embryopathy phenotype (TEP) was established for surveillance. Children with TEP born between the years 2000–2008 were monitored, and during the 2007–2008 period we clinically investigated in greater detail all cases with TEP (proactive period). The period from 1982 to 1999 was defined as the baseline period for the cumulative sum statistics. The frequency of TEP during the surveillance period, at 3.10/10,000 births (CI 95%: 2.50–3.70), was significantly higher than that observed in the baseline period (1.92/10,000 births; CI 95%: 1.60–2.20), and not uniformly distributed across different Brazilian regions. During the proactive surveillance (2007–2008), two cases of suspected TE were identified, although the two mothers had denied the use of the drug during pregnancy. Our results suggest that TEP has probably increased in recent years, which coincides with the period of greater thalidomide availability. Our proactive surveillance identified two newborns with suspected TE, proving to be a sensitive tool to detect TE. The high frequency of leprosy and the large use of thalidomide reinforce the need for a continuous monitoring of TEP across Brazil

The HLA-A, -B and -DRB1 polymorphism in a large dataset of South Brazil bone marrow donors from Rio Grande do Sul

Human leukocyte antigen (HLA) genes are very informative in population genetics studies and their variability has been widely used to reconstruct the history of geographic and/or demographic expansions of human populations. The characterization of HLA diversity at the population level is also fundamental in clinical studies, particularly for bone marrow transplantation programs. In this study, we investigated the HLA molecular variation in Rio Grande do Sul, South Brazil, in order to identify possible regional differences across this state. More than 97,000 bone marrow donors were typed at the HLA- A, -B and -DRB1 loci and analyzed by considering two kinds of subdivisions based on both self-identified ethnicity and place of residence: (a) the official geographic subdivision defined by the Brazilian Institute of Geography and Statistics and (b) known information about the colonization history of the state. HLA allele and haplotype frequencies were estimated and compared among the defined subgroups. The results indicate a lack of correlation between genetic variation and geography and thus no clear HLA genetic structure based on geographic criteria. On the other hand, major differences were observed regarding ethnicity. In addition, local populations from Rio Grande do Sul were found to be genetically similar to their corresponding parental European populations from Germany, Italy and Portugal, as documented by historical data. Overall, this study provides a thorough characterization of the HLA genetic variation in Rio Grande do Sul and a better understanding of its demographic history, being most useful for the development of more efficient strategies in bone marrow donors' recruitment

Clinical and molecular characterization of a brazilian cohort of campomelic dysplasia patients, and identification of seven new SOX9 mutations

Campomelic dysplasia (CD) is an autosomal, dominantly inherited, skeletal abnormality belonging to the subgroup of bent bone dysplasias. In addition to bowed lower limbs, CD typically includes the following: disproportionate short stature, flat face, micrognathia, cleft palate, bell-shaped thorax, and club feet. Up to three quarters of 46, XY individuals may be sex-reversed. Radiological signs include scapular and pubic hypoplasia, narrow iliac wings, spaced ischia, and bowed femora and tibiae. Lethal CD is usually due to heterozygous mutations in SOX9, a major regulator of chondrocytic development. We present a detailed clinical and molecular characterization of nine Brazilian CD patients. Infants were either stillborn (n = 2) or died shortly after birth and presented similar phenotypes. Sex-reversal was observed in one of three chromosomally male patients. Sequencing of SOX9 revealed new heterozygous mutations in seven individuals. Six patients had mutations that resulted in premature transcriptional termination, while one infant had a single-nucleotide substitution at the conserved splice-site acceptor of intron 1. No clear genotype-phenotype correlations were observed. This study highlights the diversity of SOX9 mutations leading to lethal CD, and expands the group of known genetic alterations associated with this skeletal dysplasia.Campomelic dysplasia (CD) is an autosomal, dominantly inherited, skeletal abnormality belonging to the subgroup of bent bone dysplasias. In addition to bowed lower limbs, CD typically includes the following: disproportionate short stature, flat face, micr3811420CNPQ - CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO402008/2010-3; 590148/2011-

So close, so far away: analysis of surnames in a town of twins (Cándido Godoi, Brazil)

Candido God ˆ oi is a small Brazilian town known for high rates of twin birth. In 2011, a genetic study showed that ´ this localized high rate of twin births could be explained by a genetic founder effect. Here we used isonymic analysis and surname distribution to identify population subgroups within 5316 inhabitants and 665 different surnames. Four clusters were constructed based on different twin rates (P < 0.001; MRPP test). Fisher´s α and consanguinity index showed low and high values, respectively, corresponding with observed values in isolated communities with high levels of genetic drift. Values of A and B estimators confirmed population isolation. Three boundaries were identified with Monmonier´s maximum difference algorithm (P = 0.007). Inside the isolated sections, surnames of different geographic origins, language, and religion were represented. With an adequate statistical methodology, surname analyses provided a close approximation of historic and socioeconomic background at the moment of colony settlement. In this context, the maintenance of social and cultural practices had strong implications for the population´s structure leading to drift processes in this small town, supporting the previous genetic study.Fil: de Oliveira, Marcelo Zagonel . Universidade Federal Do Rio Grande Do Sul; Brasil. Instituto Nacional de Genetica Médica Populacional; BrasilFil: Faccini, Lavínia Schüler . Universidade Federal Do Rio Grande Do Sul; Brasil. Instituto Nacional de Genetica Médica Populacional; BrasilFil: Demarchi, Dario. Universidad Nacional de Cordoba. Facultad de Filosofia y Humanidades. Museo de Antropologia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Instituto de Antropología de Córdoba; ArgentinaFil: Alfaro, Emma L.. Universidad Nacional de Jujuy. Instituto de Biologia de la Altura; ArgentinaFil: Dipierri, José E.. Universidad Nacional de Jujuy. Instituto de Biologia de la Altura; ArgentinaFil: Veronez, Mauricio R.. Universidade Do Vale Do Rio Dos Sinos; BrasilFil: Cassel, Marlise Colling . Instituto Nacional de Genetica Médica Populacional; Brasil. Universidade Federal do Rio Grande do Sul; BrasilFil: Ribeiro, Alice Tagliani. Universidade Federal Do Rio Grande Do Sul; Brasil. Instituto Nacional de Genetica Médica Populacional; BrasilFil: Matte, Ursula Silveira. Hospital de Clínicas de Porto Alegre; Brasil. Instituto Nacional de Genetica Médica Populacional; BrasilFil: Ramallo, Virginia. Universidade Federal Do Rio Grande Do Sul; Brasil. Instituto Nacional de Genetica Médica Populacional; Brasil. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin