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.

A pintura de Jesuíno do Monte Carmelo na Igreja da Ordem Terceira do Carmo em São Paulo

Pós-graduação em Artes - IA

O processo de aprendizagem e as epifanias em Os anjos, de Teolinda Gersão

Pós-graduação em Letras - IBILCE

O passado no presente: João Gilberto Noll, leitor de Álvares de Azevedo

In the mid-nineteenth century, in his fruitful years of the perhaps best-known shortest literary career, Álvares de Azevedo wrote this verse “As ondas são anjos que dormem no mar” (“The waves are angels who sleep in the sea”). In the presentation of João Gilberto Noll’s young adult novel Anjo das ondas (Angel of the waves) in 2010, Ivan Marques states that the character in the novel, Gustavo, “with his adolescent passion, and torn spirit with overflowing lyrics, could even be compared to our tropical Byron”. João Gilberto Noll establishes a connection between him and Álvares de Azevedo that invites the reader to go beyond a first reading level of his work, seeking evidence of dialogue ratification between two apparently distant writers. The subtle intertextuality exceeds the initial clue and can be detected on Noll’s theme development from the history of Gustavo, a troubled teenager in search of his identity. Noll’s affinity to Álvares de Azevedo can still be captured in his narrative texture, in voices coming from his text; however, they also reveal to be unique and original features of his literary production. An apparent exercise in style shows that each author fulfills his mission by expressing, in his own way, the feeling of his time. In addition, it shows that through aesthetic emotion, literature allows us to transcend time and space.