Molecular findings of colombian patients with type VI mucopolysaccharidosis (Maroteaux-Lamy syndrome)

Q483-89Introduction: Maroteaux–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. Results: Fourteen 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.900TNG, and c.1531_1553del) and 43% had been previously reported (p.G144R, p.W322*, p.G302R, p.C447F, p.L128del, and c.1143-1GNC). 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. Conclusions: Most of the Colombian patients in this study had private mutations

Analysis of the mutational spectrum of Duchenne muscular dystrophy in a group of Colombian patients

Introducción: La distrofia muscular de Duchenne (OMIM: 310200, ORPHA: 98896) es una mio-patía hereditaria, recesiva, ligada a X. Es el desorden neuromuscular de etiología genética más frecuente, con una incidencia de uno por cada 3.500 hombres y una prevalencia global de 4,78 por cada 100.000 personas. Métodos: Se llevó a cabo una evaluación clínica de 63 pacientes con distrofia muscular de Duchenne en un centro de referencia de Colombia. Se realizó a todos los sujetos un análisis molecular a través de MLPA y una secuenciación masiva en paralelo. Resultados; En 47 de los 62 sujetos (75%) se detectaron variantes tipo deleción/duplicación de exones en el gen de la distrofina, mediante MLPA. Se encontraron 33 probandos con deleciones (53,2%) y 14 casos de duplicaciones (22,5%) de uno o más exones. El estudio de secuenciación del gen DMD por la técnica de secuenciación masiva en paralelo fue realizado en 15 individuos (24,2%) con MLPA negativo. Se evidenciaron mutaciones sin sentido (nonsense) en 6 casos (9,6%), mutaciones que afectan el marco de lectura en 7 casos (11%) y mutaciones que afectan el splicing en 2 probandos (3,2%). No se encontraron mutaciones missense. Las variantes se distribuyeron a lo largo del gen y se encontraron 5 variantes que no habían sido previamente reportadas, identificadas en 7 individuos. Conclusiones: El diagnóstico molecular de mutaciones puntuales a través de secuenciación masiva paralela permitió alcanzar de manera eficiente la confirmación diagnóstica, definiendo para los casos negativos para deleción/duplicación, la asesoría adecuada y la implementación de un manejo terapéutico apropiado.Q4Artículo original137–146Introduction; Muscular dystrophy of Duchenne (OMIM: 310200, ORPHA: 98896) is a recessive X-linked primary myopathy. It is the most frequent neuromuscular disorder of genetic etiology, with an incidence of one per 3,500 men and an overall prevalence of 4.78 per 100.000 people. Methods; A clinical evaluation of 63 patients with Duchenne muscular dystrophy was carried out in a Colombian reference center. We performed all the subjects, molecular analysis through MLPA and massive sequencing in parallel. Results; In 47 of the 62 subjects (75%), deletion/duplication variants of exons were detected in the dystrophin gene, using MLPA. We found 33 probands with deletions (53.2%) and 14 cases of duplications (22.5%) of one or more exons. The sequencing study of the DMD gene by the mass sequencing technique in parallel was performed in 15 individuals (24.2%) with negative MLPA. There were nonsense mutations in 6 cases (9.6%), mutations affecting the reading frame in 7 cases (11%) and mutations affecting splicing in 2 cases (3.2%). No missense mutations were found. The variants were distributed throughout the gene, and five variants were found that had not been previously reported, identified in 7 individuals. Conclusions. The molecular diagnosis of point mutations through massively parallel sequencing allowed to reach the diagnostic confirmation efficiently, defining for the negative cases for deletion/duplication, the adequate advice and the implementation of appropriate therapeutic management

Preeclampsia association of placental nucleotide variations in eNOS, VEGFA, and FLT-1 genes in Latin American pregnant women

Introduction: Preeclampsia is a leading cause of maternal and fetal morbidity in low- and middle-income countries, including those in Latin America. Placental vascular alterations are crucial in the pathophysiology of preeclampsia and few studies have evaluated nucleotide variations on genes associated with vascular regulation in the human placenta. This study aimed to evaluate whether placental nucleotide variations on eNOS, VEGFA, and FLT-1 genes are more frequently associated with preeclampsia in the Latin American population. Methods: This case-control study included placental tissue from 88 controls and 82 cases that were genotyped through Taqman probes for eNOS, VEGFA, and FLT-1 genes. The intergroup comparisons were analyzed with the Mann-Whitney U test. Genotype and allele frequencies were compared by the X2 test. The association between the nucleotide variants with preeclampsia was evaluated through logistic regression analysis. Results: A significant association was observed for VEGFA SNV rs2010963 (OR 1.95; CI 95% 1.13–3.37), after adjusting for population substructure. The allele combination T, G, G, C, C, C (rs2070744, rs1799983, rs2010963, rs3025039, rs699947 and rs4769613 respectively), showed a negative association with preeclampsia (OR 0.08; CI 95% 0.01–0.93). results. Discussion: Placental SNV rs2010963 in the VEGFA gene was a risk factor for preeclampsia, while the allele combination T, G, G, C, C, C may represent potential protective factors for preeclampsia within Latin American women.Fil: Macías Salas, Alejo. INSTITUTO POLITÉCNICO NACIONAL (IPN);Fil: Sosa Macías, Martha. INSTITUTO POLITÉCNICO NACIONAL (IPN);Fil: Barragán Zúñiga, Laura Jazel. INSTITUTO POLITÉCNICO NACIONAL (IPN);Fil: Blanco Castañeda, Ricardo. INSTITUTO POLITÉCNICO NACIONAL (IPN);Fil: Damiano, Alicia Ermelinda. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; ArgentinaFil: Garcia Robles, Reggie. Pontificia Universidad Javeriana; ColombiaFil: Ayala Ramírez, Paola. Pontificia Universidad Javeriana; ColombiaFil: Bueno Sánchez, Julio. Universidad de Antioquia; ColombiaFil: Giachini, Fernanda Regina. Universidade Federal do Mato Grosso do Sul; BrasilFil: Escudero, Carlos. Universidad del Bio Bio; ChileFil: Galaviz Hernández, Carlos. INSTITUTO POLITÉCNICO NACIONAL (IPN)

The limited knowledge of placental damage due to neglected infections: ongoing problems in Latin America

The placenta works as a selective barrier, protecting the fetus from potential infections that may affect the maternal organism during pregnancy. In this review, we will discuss several challenging infections that are common within Latin American countries and that may affect the maternal-fetal interface and pose risks to fetal development. Specifically, we will focus on emerging infectious diseases including the arboviruses, malaria, leishmaniasis, and the bacterial foodborne disease caused by Shiga toxinproducing Escherichia coli. We will also highlight some topics of interest currently being studied by research groups that comprise an international effort aimed at filling the knowledge gaps in this field. These topics address the relationship between exposure to microorganisms and placental abnormalities, congenital anomalies, and complications of pregnancy.Fil: Moreti Ribeiro, Isabel. Universidade Federal do Mato Grosso do Sul; BrasilFil: Souza Souto, Paula Cristina. Universidade Federal do Mato Grosso do Sul; BrasilFil: Borbely, Alexandre U.. Universidade Federal de Alagoas; BrasilFil: Lopez Lira Tanabe, Eloiza. Universidade Federal de Alagoas; BrasilFil: Cadavid, Angela. Universidad de Antioquia; ColombiaFil: Alvarez, Angela M.. Universidad de Antioquia; ColombiaFil: Bueno, Julio. Universidad de Antioquia; ColombiaFil: Agudelo, Olga. Universidad de Antioquia; ColombiaFil: Garcia Robles, Reggie. Pontificia Universidad Javeriana; ColombiaFil: Ayala Ramirez, Paola. Pontificia Universidad Javeriana; ColombiaFil: Sacerdoti, Flavia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; ArgentinaFil: Szasz, Theodora. Augusta University; Estados UnidosFil: Damiano, Alicia Ermelinda. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; ArgentinaFil: Ibarra, Cristina Adriana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; ArgentinaFil: Escudero, Carlos. Universidad del Bio Bio; ChileFil: Lima, Víctor V.. Universidade Federal do Mato Grosso do Sul; BrasilFil: Giachini, Fernanda R.. Universidade Federal do Mato Grosso do Sul; Brasi