Clinical and molecular phenotype of Aicardi-Goutières syndrome

Aicardi-Goutières syndrome (AGS) is a genetic encephalopathy whose clinical features mimic those of acquired in utero viral infection. AGS exhibits locus heterogeneity, with mutations identified in genes encoding the 3′→5′ exonuclease TREX1 and the three subunits of the RNASEH2 endonuclease complex. To define the molecular spectrum of AGS, we performed mutation screening in patients, from 127 pedigrees, with a clinical diagnosis of the disease. Biallelic mutations in TREX1, RNASEH2A, RNASEH2B, and RNASEH2C were observed in 31, 3, 47, and 18 families, respectively. In five families, we identified an RNASEH2A or RNASEH2B mutation on one allele only. In one child, the disease occurred because of a de novo heterozygous TREX1 mutation. In 22 families, no mutations were found. Null mutations were common in TREX1, although a specific missense mutation was observed frequently in patients from northern Europe. Almost all mutations in RNASEH2A, RNASEH2B, and RNASEH2C were missense. We identified an RNASEH2C founder mutation in 13 Pakistani families. We also collected clinical data from 123 mutation-positive patients. Two clinical presentations could be delineated: an early-onset neonatal form, highly reminiscent of congenital infection seen particularly with TREX1 mutations, and a later-onset presentation, sometimes occurring after several months of normal development and occasionally associated with remarkably preserved neurological function, most frequently due to RNASEH2B mutations. Mortality was correlated with genotype; 34.3% of patients with TREX1, RNASEH2A, and RNASEH2C mutations versus 8.0% RNASEH2B mutation-positive patients were known to have died (P = .001). Our analysis defines the phenotypic spectrum of AGS and suggests a coherent mutation-screening strategy in this heterogeneous disorder. Additionally, our data indicate that at least one further AGS-causing gene remains to be identified. © 2007 by The American Society of Human Genetics. All rights reserved.

Regional Panorama: Latin America. Megacities and sustainability

Includes bibliography

Las tendencias principales del comercio, la política comercial y los acuerdos de integración de los países de la Asociación de Estados del Caribe (AEC)

Incluye Bibliografía

Las condiciones de acceso a los mercados de bienes: algunos problemas pendientes

Incluye Bibliografía

Los procesos de integración de los países de América Latina y el Caribe 2000-2001: avances, retrocesos y temas pendientes

Incluye Bibliografía

Población y mano de obra de Chile: 1930-1975

Incluye Bibliografía

Análisis demográfico de la situación educativa en América Latina

Incluye Bibliografía

Síntesis del Seminario sobre la Inserción Económica Internacional de la Comunidad Andina

Incluye Bibliografía

Tendencias de la urbanizacion, inversion de la polarizacion y politica espacial en Colombia

Incluye Bibliografía

Tendencias de la urbanización, inversión de la polarización y política espacial en Colombia

Incluye Bibliografía

Main trade trends, trade policy and integration in the greater Caribbean

Includes bibliography

Acceso a los mercados de bienes en el nuevo contexto internacional: desafíos para América Latina y el Caribe

Incluye Bibliografía

Adaptation to climate change in megacities of Latin America: Regional Learning Network of the research project ClimateAdaptationSantiago (CAS)

The main objective of this publication is to document the current state of urban climate change adaptation practice in Latin America. It is a summary of the three workshops of the Regional Learning Network that was set up under the ClimateAdaptationSantiago project (CAS), encompassing six large Latin American cities (Bogotá, Buenos Aires, Lima, Mexico City, São Paulo and Santiago). It aims to synthesize information on the manifestations and impacts of climate change in those Latin American cities that participated in the network, and above all, governance in the form of concrete actions. The publication is based on information obtained from the participants in the three workshops, but also includes additional scientific input and reflections by the editors. All of this information makes a major contribution to highlighting the different paths these six cities are pursuing in response to climate change. To that end, the publication discusses the various courses of action on climate change adaptation, with the aim of learning from these cases and highlighting practical examples.