RESUMEN
We report a 5-generation family with phenotypically diverse neurodegenerative disease including relentlessly progressive choreoathetoid movements, dysarthria, dysphagia, spastic paralysis, and behavioral dementia in descendants of a 67-year-old woman with amyotrophic lateral sclerosis. Disease onset varied with gender, occurring in male children and adult women. Exome sequence analyses revealed a novel mutation (c.1490C>T, p.P497L) in the ubiquilin-2 gene (UBQLN2) with X-linked inheritance in all studied affected individuals. As ubiquilin-2-positive inclusions were identified in brain, we suggest that mutant peptide predisposes to protein misfolding and accumulation. Our findings expand the spectrum of neurodegenerative phenotypes caused by UBQLN2 mutations.
Asunto(s)
Proteínas de Ciclo Celular/genética , Heterogeneidad Genética , Trastornos Heredodegenerativos del Sistema Nervioso/diagnóstico , Trastornos Heredodegenerativos del Sistema Nervioso/genética , Mutación/genética , Ubiquitinas/genética , Proteínas Adaptadoras Transductoras de Señales , Adolescente , Adulto , Anciano , Proteínas Relacionadas con la Autofagia , Preescolar , Femenino , Genes Dominantes , Humanos , Masculino , Linaje , Pliegue de Proteína , Adulto JovenRESUMEN
E.C. Seguin was one of the early, influential 19th-century neurologists who participated in the development of neurology as a specialty in the United States. Born in France, but raised from early childhood in the United States, Seguin published widely, developed a high-profile New York City practice, and was named Clinical Professor of Diseases of the Mind and Nervous System at the College of Physicians and Surgeons (New York) in 1874. Typical of the era, he studied neurologic disorders, but also several conditions that today would be considered in the realm of psychiatry. One of his seminal papers was titled "The treatment of mild cases of melancholia at home" (1876). Contrary to the widespread practice of isolating patients in either rest homes or asylums, Seguin introduced and formalized treatment of depression within the household. Against this academic backdrop, Seguin returned home on October 31, 1882, to discover that his own wife, afflicted with long-standing depression and treated at home, had committed suicide after murdering their 3 children. The grim dichotomy between the confidently written paper and the reality of the treatment failure is a neurologic lesson in humility regarding diseases and their unpredictable outcomes.
Asunto(s)
Trastorno Depresivo/historia , Psiquiatría Forense/historia , Homicidio/historia , Neurología/historia , Suicidio/historia , Trastorno Depresivo/terapia , Femenino , Historia del Siglo XIX , Humanos , Masculino , Ciudad de Nueva York , EspososRESUMEN
Charcot and Pasteur were scientific contemporaries, but their relationship has not been extensively studied. We analyzed available source documents from the Charcot Library, Bibliothèque Nationale, Institute Pasteur, and Pasteur Library. These documents demonstrate that in spite of geographical proximity, international and local recognition, Charcot and Pasteur largely pursued their careers independent of one another. Although the Paris scientific climate was one of active debate, Pasteur's and Charcot's interactions remained distanced but mutually respectful and did not descend into rivalry or contention. With different primary interests and different etiological views, side by side, they exemplified two models of French medicine at the close of the nineteenth century: medical scientist and scientific physician.