RESUMO
PNPLA6 mutations, known to be associated with the development of motor neuron phenotypes, have recently been identified in families with Boucher-Neuhäuser syndrome. Boucher-Neuhäuser is a rare autosomal recessive syndrome characterized by the co-occurrence of cerebellar ataxia, hypogonadotropic hypogonadism, and chorioretinal dystrophy. Gait ataxia in Boucher-Neuhäuser usually manifests before early adulthood, although onset in the third or fourth decade has also been reported. However, given the recent identification of PNPLA6 mutations as the cause of this condition, the determining factors of age of symptom onset still need to be established. Here, we have identified a sporadic Boucher-Neuhäuser case with late-onset gait ataxia and relatively milder retinal changes due to compound heterozygous PNPLA6 mutations. Compound heterozygosity was confirmed by cloning and sequencing the patient's genomic DNA from coding exons 26-29. Furthermore, both mutations (one novel and one known) fell in the phospholipase esterase domain, where most pathogenic mutations seem to cluster. Taken together, we herein confirm PNPLA6 mutations as the leading cause of Boucher-Neuhäuser syndrome and suggest inquiring about a history of hypogonadism or visual changes in patients presenting with late-onset gait ataxia. We also advocate for neuroophthalmologic evaluation in suspected cases.
Assuntos
Ataxia/genética , Hipogonadismo/genética , Fosfolipases/genética , Distrofias Retinianas/genética , Ataxias Espinocerebelares/genética , Idade de Início , Éxons , Feminino , Heterozigoto , Humanos , Hipogonadismo/patologia , Hipogonadismo/fisiopatologia , Pessoa de Meia-Idade , Mutação , Degeneração Retiniana/genética , Distrofias Retinianas/patologia , Distrofias Retinianas/fisiopatologia , Ataxias Espinocerebelares/patologia , Ataxias Espinocerebelares/fisiopatologiaRESUMO
Five investigators familiar with gastric ulcer disease in horses met to establish a scoring system that could be utilised in future studies. Slides of gastric lesions were viewed and discussed and a scoring system established that required the nonglandular and glandular portions of the stomach to be graded separately. Each portion of the stomach (glandular and nonglandular) received a score for number of ulcers present and a score for severity of ulcers which resulted in each stomach receiving 4 separate scores. After the grading system was developed, each investigator independently graded 16 horses with gastric ulcer disease that had been previously recorded on video tape. The results of each investigator's scores were then compared. There was a variability between observers in the scores for severity of both nonglandular and glandular lesions but the variability was not significant. The variability between observers for the number of glandular lesions was also not significant. This implied that there was consistency between the 5 observers in the way severity of lesions was scored and the number of glandular lesions. However, there was a significant variability between observers for the number of nonglandular lesions which implied agreement on this observation was more variable.
Assuntos
Doenças dos Cavalos/patologia , Úlcera Gástrica/veterinária , Animais , Gastroscopia/métodos , Gastroscopia/veterinária , Cavalos , Variações Dependentes do Observador , Índice de Gravidade de Doença , Estômago/patologia , Úlcera Gástrica/patologiaRESUMO
The paper describes procedures for contrasting actions taken by crises intervention outreach workers and consumers with administrative policies. The data used to exemplify the procedures came from the outreach projects of six county MH/MR programs in Central Pennsylvania during the year following the flood caused by Hurricane Agnes, in 1972. The procedure identifies and counts the ways through which consumers entered the outreach process; the major outreach worker decision; and the immediate disposition of each consumer's case. The six county MH/MR program administrators were asked to consider program policies and show how they would ideally expect 1,000 hypothetical consumers to come into, to be processed through, and to be referred out of their respective outreach programs. Contrasts of the ideal and actual consumer data, along with consumer follow-up questionnaires, provided the basis for evaluating the six county MH/MR program outreach projects. These experiences provided the basis for a generalized model of evaluating crises intervention activities.