Purpose: Hereditary Breast and Ovarian Cancer (HBOC) syndrome is responsible for ∼5-10% of all diagnosed breast and ovarian cancers. Breast cancer is the most common malignancy and the leading cause of cancer-related mortality among women in Latin America (LA). The main objective of this study was to develop a comprehensive understanding of the genomic epidemiology of HBOC throughout the establishment Oliver et al. Latin American HBOC Study of The Latin American consortium for HBOC-LACAM, consisting of specialists from 5 countries in LA and the description of the genomic results from the first phase of the study. Methods: We have recruited 403 individuals that fulfilled the criteria for HBOC from 11 health institutions of Argentina, Colombia, Guatemala, Mexico and Peru. A pilot cohort of 222 individuals was analyzed by NGS gene panels. One hundred forty-three genes were selected on the basis of their putative role in susceptibility to different hereditary cancers. Libraries were sequenced in MiSeq (Illumina, Inc.) and PGM (Ion Torrent-Thermo Fisher Scientific) platforms. Results: The overall prevalence of pathogenic variants was 17% (38/222); the distribution spanned 14 genes and varied by country. The highest relative prevalence of pathogenic variants was found in patients from Argentina (25%, 14/57), followed by Mexico (18%, 12/68), Guatemala (16%, 3/19), and Colombia (13%, 10/78). Pathogenic variants were found in BRCA1 (20%) and BRCA2 (29%) genes. Pathogenic variants were found in other 12 genes, including high and moderate risk genes such as MSH2, MSH6, MUTYH, and PALB2. Additional pathogenic variants were found in HBOC unrelated genes such as DCLRE1C, WRN, PDE11A, and PDGFB. Conclusion: In this first phase of the project, we recruited 403 individuals and evaluated the germline genetic alterations in an initial cohort of 222 patients among 4 countries. Our data show for the first time in LA the distribution of pathogenic variants in a broad set of cancer susceptibility genes in HBOC. Even though we used extended gene panels, there was still a high proportion of patients without any detectable pathogenic variant, which emphasizes the larger, unexplored genetic nature of the disease in these populations.

Introducción. Las mucopolisacaridosis son enfermedades poco frecuentes de depósito lisosómico de glucosaminoglucanos, con datos variables sobre su incidencia en diferentes países a nivel mundial. En Latinoamérica hay reportes de frecuencias en Brasil, pero en Colombia la información es escasa. Objetivos. Estimar las frecuencias de las mucopolisacaridosis mediante un estudio retrospectivo en los departamentos de Cundinamarca y Boyacá, y estimar la agregación espacial de los casos en estos mismos departamentos. Materiales y métodos. Se revisaron los registros de pacientes de diferentes instituciones de referencia para enfermedades genéticas, así como los registros de nacimientos vivos entre 1998 y 2007. Con base en ellos, se estimaron las frecuencias para cada tipo de mucopolisacaridosis. Se analizó la agregación espacial de los casos utilizando el programa SaTScan™. Resultados. La frecuencia combinada para todas las mucopolisacaridosis fue de 1,98 casos por 100.000 nacidos vivos. La mayor frecuencia fue para la de tipo IV, con 0,68 casos por 100.000 nacidos vivos, mientras que la III fue la menor, con 0,17 casos. Se encontraron tres posibles áreas de agregación espacial para las mucopolisacaridosis I, III y IV. Conclusión. La frecuencia combinada para todas las mucopolisacaridosis se encuentra dentro de los rangos reportados en la literatura científica, siendo la de tipo IV la más frecuente y la de tipo VII la menos frecuente. Aunque los datos aquí reportados podrían corresponder a un subregistro, dadas las dificultades inherentes a la recolección de la información en nuestro país, consideramos que son un estimativo válido de las frecuencias de estas enfermedades.Palabras clave: mucopolisacaridosis/epidemiología, errores innatos del metabolismo, enfermedades por almacenamiento lisosómico, análisis por conglomerados. doi: http://dx.doi.org/10.7705/biomedica.v32i4.574 Estimation of the mucopolysaccharidoses frequencies and cluster analysis in the Colombian provinces of Cundinamarca and BoyacáIntroduction. Mucopolysaccharidoses are a group of infrequent disorders caused by the lysosomal deposit of glycosaminoglycans. Its incidence is quite variable among thecountries where it has been documented. In Brazil, disorder frequencies have been reported, but in Colombia information on them is scarce. Objectives. The frequency and spatial aggregations of the mucopolysaccharidoses were estimated by a retrospective study in two central Colombian provinces. Materials and methods. The records of patients and live newborns between 1998-2007 were reviewed from several reference institutions for genetic diseases. From these records, the frequencies for each mucopolysaccharidosis were estimated. The spatial aggregation of the cases was analyzed using the SaTScan software. Results. The combined frequency for all the mucopolysaccharidoses was 1.98 cases per 100,000 live newborns. MPS IV had the highest frequency with 0.68 cases per 100,000 live newborns and MPS III showed a lower frequency of 0.17/100,000. Three spatial aggregation a...

In Latin America and the Caribbean, hypertensive pregnancy disorders are responsible for almost 26% of all maternal deaths [1] and, in Colombia, they account for 59% of all severe maternal morbidity (SMM) cases, and 59.7% of all SMM cases in adolescents [2]. One of the most important hypertensive pregnancy disorders is preeclampsia (PE). Lives can be saved, if PE is prevented, or detected early and properly managed. Prevention and detection depend on identifying the risk factors associated with PE, and, as these have been shown vary by population, they should be determined on a population-by-population basis. The following study utilized the nested case-control model to evaluate 45 potential PE risk factors of a cohort in Bogotá, Colombia, making it perhaps the most comprehensive study of its kind in Colombia. It found PE to have a statistically significant association with 7 of the 45 factors evaluated: 1) pre-gestational BMI >30 kg/m 2 , 2) pregnancy weight gain >12 kg, 3) previous history preeclampsia/eclampsia, 4) previous history of IUGR-SGA (Intrauterine Growth Restriction-Small for Gestational Age), 5) maternal age <20 or ≥35 years (20–34 was not associated), and 6) family history of diabetes. Finally, prenatal consumption of folic acid was found to lower the risk of PE. We recommend that, in Colombia, factors 1–6 be used to identify at risk mothers during pregnancy check-ups; that mothers be encouraged to take folic acid during pregnancy; and, that Colombia's health system and public policy address the problem of pregestational obesity.

IntroductionMaroteaux–Lamy syndrome, or mucopolysaccharidosis (MPS) type VI, is an autosomal recessive lysosomal storage disease caused by a deficient activity of the enzyme arylsulfatase B (ARSB), required to degrade dermatan sulfate. The onset and progression of the disease vary, producing a spectrum of clinical presentation. So far, 133 mutations have been reported. The aim of this study is to determine the mutations in the ARSB gene that are responsible for this disease in Colombian patients.ResultsFourteen patients with clinical manifestations and biochemical diagnosis of MPS VI were studied, including two siblings. The 8 exons of the gene were directly sequenced from patients' DNA, and 14 mutations were found. 57% of these mutations had not been previously reported (p.H111P, p.C121R, p.G446S, p.*534W, p.S334I, p.H147P, c.900T > G, and c.1531_1553del) and 43% had been previously reported (p.G144R, p.W322*, p.G302R, p.C447F, p.L128del, and c.1143-1G > C). Of the previously reported mutations, 80% have been associated with severe phenotypes and 20% with intermediate-severe phenotypes. Bioinformatic predictions indicate that the new mutations reported in this paper are also highly deleterious.ConclusionsMost of the Colombian patients in this study had private mutations.