RESUMEN
Neurodegenerative disorders such as Parkinson and Alzheimer disease cause motor and cognitive dysfunction and belong to a heterogeneous group of common and disabling disorders. Although the complex molecular pathophysiology of neurodegeneration is largely unknown, major advances have been achieved by elucidating the genetic defects underlying mendelian forms of these diseases. This has led to the discovery of common pathophysiological pathways such as enhanced oxidative stress, protein misfolding and aggregation and dysfunction of the ubiquitin-proteasome system. Here, we describe loss-of-function mutations in a previously uncharacterized, predominantly neuronal P-type ATPase gene, ATP13A2, underlying an autosomal recessive form of early-onset parkinsonism with pyramidal degeneration and dementia (PARK9, Kufor-Rakeb syndrome). Whereas the wild-type protein was located in the lysosome of transiently transfected cells, the unstable truncated mutants were retained in the endoplasmic reticulum and degraded by the proteasome. Our findings link a class of proteins with unknown function and substrate specificity to the protein networks implicated in neurodegeneration and parkinsonism.
Asunto(s)
Adenosina Trifosfatasas/genética , Demencia/etiología , Lisosomas/enzimología , Mutación , Trastornos Parkinsonianos/genética , ATPasas de Translocación de Protón/genética , Adenosina Trifosfatasas/metabolismo , Demencia/genética , Retículo Endoplásmico/enzimología , Femenino , Humanos , Masculino , Mesencéfalo/enzimología , Mesencéfalo/patología , Neuronas/enzimología , Neuronas/patología , Trastornos Parkinsonianos/complicacionesRESUMEN
We here report a rather novel syndrome of dysmorphic features, short stature, microcephaly, alopecia, psychomotor retardation, retinitis pigmentosa and secondary amenorrhoea. This may present a new complex multisystem disorder distinct from those reported in the literature and we propose the acronym D-CHRAMPS for this novel disorder.
Asunto(s)
Alopecia/genética , Hipogonadismo/genética , Microcefalia/genética , Trastornos Psicomotores/genética , Retinitis Pigmentosa/genética , Adolescente , Estatura , Femenino , Humanos , SíndromeRESUMEN
We report a case of a 29-year-old female patient with atypical magnetic resonance image appearance of multiple sclerosis simulating brain tumor on magnetic resonance images, that proved to be a demyelinating disease on brain biopsy. Steroid pulse therapy produced regression of the lesions on magnetic resonance images.
