Clusters of genetic diseases in Brazil.

The aim of this paper is to present a database of isolated communities (CENISO) with high prevalence of genetic disorders or congenital anomalies in Brazil. We used two strategies to identify such communities: (1) a systematic literature review and (2) a "rumor strategy" based on anecdotal accounts. All rumors and reports were validated in a stepwise process. The bibliographical search identified 34 rumors and 245 rumors through the rumor strategy, and 144 were confirmed. A database like this one presented here represents an important tool for the planning of health priorities for rare diseases in low- and middle-income countries with large populations.

Uniparental ancestry markers in Chilean populations.

The presence of Native Americans, Europeans, and Africans has led to the development of a multi-ethnic, admixed population in Chile. This study aimed to contribute to the characterization of the uniparental genetic structure of three Chilean regions. Newborns from seven hospitals in Independencia, Providencia, Santiago, Curicó, Cauquenes, Valdívia, and Puerto Montt communes, belonging to the Chilean regions of Santiago, Maule, and Los Lagos, were studied. The presence of Native American mitochondrial DNA (mtDNA) haplogroups and two markers present in the non-recombinant region of the Y chromosome, DYS199 and DYS287, indicative of Native American and African ancestry, respectively, was determined. A high Native American matrilineal contribution and a low Native American and African patrilineal contributions were found in all three studied regions. As previously found in Chilean admixed populations, the Native American matrilineal contribution was lower in Santiago than in the other studied regions. However, there was an unexpectedly higher contribution of Native American ancestry in one of the studied communes in Santiago, probably due to the high rate of immigration from other regions of the country. The population genetic sub-structure we detected in Santiago using few uniparental markers requires further confirmation, owing to possible stratification for autosomal and X-chromosome markers.

Descriptive analysis of high birth prevalence rate geographical clusters of congenital anomalies in South America.

BACKGROUND: The birth prevalence rate (BPR) of congenital anomalies (CAs) is heterogeneous and exhibits geographical and sociocultural variations throughout the world. In South America (SA), high birth prevalence regions of congenital anomalies have been observed. The aim of this study was to identify, describe, and characterize geographical clusters of congenital anomalies in SA. METHODS: This observational descriptive study is based on clinical epidemiological data registered by the Latin-American Collaborative Study of Congenital Malformations network. Between 1995 and 2012, a total of 25,082 malformed newborns were ascertained from 2,557,424 births at 129 hospitals in SA. The spatial scan statistic was used to determine geographical regions with high BPR of CAs. The BPR was obtained with a Poisson regression model. Odds ratios were estimated for several risk factors inside the geographical clusters. RESULTS: We confirmed the existence of high BPR regions of CAs in SA. Indicators of low socioeconomic conditions, such as a low maternal education, extreme age childbearing, infectious diseases, and medicine use during pregnancy were detected as risk factors inside these regions. Native and African ancestries with high frequency of consanguineous marriages could explain partially these high BPR clusters. CONCLUSION: The recognition of clusters could be a starting point in the identification of susceptibility genes associated with the occurrence of CA in high BPR regions.

Molecular analysis of holoprosencephaly in South America.

Holoprosencephaly (HPE) is a spectrum of brain and facial malformations primarily reflecting genetic factors, such as chromosomal abnormalities and gene mutations. Here, we present a clinical and molecular analysis of 195 probands with HPE or microforms; approximately 72% of the patients were derived from the Latin American Collaborative Study of Congenital Malformations (ECLAMC), and 82% of the patients were newborns. Alobar HPE was the predominant brain defect in almost all facial defect categories, except for patients without oral cleft and median or lateral oral clefts. Ethmocephaly, cebocephaly, and premaxillary agenesis were primarily observed among female patients. Premaxillary agenesis occurred in six of the nine diabetic mothers. Recurrence of HPE or microform was approximately 19%. The frequency of microdeletions, detected using Multiplex Ligation-dependant Probe Amplification (MLPA) was 17% in patients with a normal karyotype. Cytogenetics or QF-PCR analyses revealed chromosomal anomalies in 27% of the probands. Mutational analyses in genes SHH, ZIC2, SIX3 and TGIF were performed in 119 patients, revealing eight mutations in SHH, two mutations in SIX3 and two mutations in ZIC2. Thus, a detailed clinical description of new HPE cases with identified genetic anomalies might establish genotypic and phenotypic correlations and contribute to the development of additional strategies for the analysis of new cases.

Effects of folic acid fortification on spina bifida prevalence in Brazil.

BACKGROUND: To assess spina bifida birth prevalence changes after folic acid fortification of wheat and maize flours began in Brazil in June 2004. METHODS: Cross-sectional study of Brazilian live births in 2004 and 2006. Spina bifida birth prevalence from the Live Births Information System (SINASC: Sistema de Informações sobre Nascidos Vivos) in a prefortified period was compared to a period fortified with folic acid in each state. Observed prevalence rates in 2004 were used to calculate the expected prevalence rates in 2006 under the null hypothesis that both were similar. The observed/expected (O/E) ratios were tested by two-tailed Z-test. To minimize ascertainment differences among states, the O/E ratio of each one of the 27 Brazilian states was adjusted for the number of births with the Mantel-Haenszel statistic. RESULTS The reduction in spina bifida birth prevalence in 2006 was 39% (O/E = 0.61; 95% confidence interval [CI], 0.55-0.67), and 40% (O/E = 0.60; 95% CI, 0.53-0.68), after adjusting for state birth number. This reduction was significant (p < 0.0001), and heterogeneous among states (χ(2) = 72.96; p < 0.0001). CONCLUSIONS: Using SINASC data, there was a significant reduction in spina bifida birth prevalence in Brazil, probably related to the folic acid food fortification program.

Beare-Stevenson cutis gyrata syndrome: A new case of a c.1124C↷G (Y375C) mutation in the FGFR2 gene.

Beare-Stevenson syndrome (BSS) (MIM#123790) is a rare disorder characterized by craniofacial anomalies and cutis gyrata associated with anogenital anomalies and prominent umbilical stump. There are few reports on the syndrome, and molecular analysis has revealed the involvement of two closely spaced mutations within the FGFR2 gene: c.1115C↷G (p.S372C) and c.1124C↷G (p.Y375C). We herein describe a new case of a c.1124C↷G mutation in a BSS patient.

New cases of thalidomide embryopathy in Brazil.

Thalidomide is the best known human teratogen. Although withdrawn from the market in 1961, thalidomide was remarketed after 1965 in several countries, for the treatment of erythema nodosum leprosum. Thalidomide has a potent immunomodulatory property and has now a number of approved and off-label uses in dermatologic, oncologic, infectious and gastrointestinal conditions. In the U.S., FDA approved the use of thalidomide in 1998, but no cases of thalidomide embriophaty were registered after that. Since 1996 no new cases were reported in Latin America. However, the Teratogen Information Service (TIS) Porto Alegre, recorded three new cases of thalidomide embriophaty born in Brazil since 2005. Considering that these three cases were not registered through a systematic surveillance system, but that came to our attention through a series of coincidental random events, it can be assumed that the actual occurrence of affected babies by thalidomide continues being as frequent as denounced ten years ago.

Complex segregation analysis of 1,792 cleft lip and palate families in South America: 1967-1997.

Although several studies have demonstrated familial aggregation of nonsyndromic cleft lip with or without cleft palate (CL/P), its model of inheritance remains uncertain. We report the results of complex segregation analysis performed in South American families with a newborn affected with CL/P. Families of 1,792 consecutive newborns affected with CL/P and registered during the period 1967 to 1997 were studied. A model that did not include a major locus was the best-fitting model for CL/P families. This result is in agreement with previous studies which showed a significant association of several putative susceptibility loci and CL/P, indicating that the genes involved in CL/P are likely to have only a very modest impact on disease risk.

Complex segregation analysis of 1, 792 cleft lip and palate families in South America: 1967-1997

Although several studies have demonstrated familial aggregation of nonsyndromic cleft lip with or without cleft palate (CL/P), its model of inheritance remains uncertain. We report the results of complex segregation analysis performed in South American families with a newborn affected with CL/P. Families of 1,792 consecutive newborns affected with CL/P and registered during the period 1967 to 1997 were studied. A model that did not include a major locus was the best-fitting model for CL/P families. This result is in agreement with previous studies which showed a significant association of several putative susceptibility loci and CL/P, indicating that the genes involved in CL/P are likely to have only a very modest impact on disease risk

Informe final de la asesoria sobre monitorización de malformaciones congénitas del 15 de febrero al 14 de marzo de 1981 / sss

Los objetivos de la asesoria fueron: Presentar a las autoridades nacionales de salud un método para detectar la prevalencia de malformaciones congénitas con una vigilancia basada en varias maternidades del país. Diseñar los formularios a utilizarse en esta vigilancia. Contactar a los responsables de las maternidades elegidas por las autoridades para participar del estudio e introducir la mecánica de la vigilancia