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Your search keyword '"Gahl, W.A"' showing total 37 results
Start Over Author "Gahl, W.A" Publication Type Academic Journals
37 results on '"Gahl, W.A"'

9. Bayesian model of disease progression in GNE myopathy.

Author

Quintana, M., Shrader, J., Slota, C., Joe, G., McKew, J.C., Fitzgerald, M., Gahl, W.A., Berry, S., and Carrillo, N.

Subjects
DISEASE progression, MUSCULAR dystrophy, RESEARCH funding, PROBABILITY theory, LONGITUDINAL method, ALGORITHMS
Abstract

One Sentence Summary: A Bayesian repeated measures model based on quantitative muscle strength data from a prospective Natural History Study was developed to determine disease progression and design clinical trials for GNE myopathy, a rare and slowly progressive muscle disease. GNE myopathy is a rare muscle disease characterized by slowly progressive weakness and atrophy of skeletal muscles. To address the significant challenges of defining the natural history and designing clinical trials for GNE myopathy, we developed a Bayesian latent variable repeated measures model to determine disease progression. The model is based on longitudinal quantitative muscle strength data collected as part of a prospective Natural History Study. The GNE Myopathy Progression Model provides an understanding of disease progression that would have otherwise required a natural history of unfeasible duration. "Disease age," the model-generated measure of disease progression, highly correlates with a variety of clinical, functional and patient-reported outcomes. With the incorporation of a treatment effect parameter to the GNE Disease Progression Model, we describe a novel GNE Myopathy Disease Modification Analysis that significantly increases power and reduces the number of subjects required to test the effectiveness of novel therapies when compared to more traditional analysis methods. The GNE Myopathy Disease Progression Model and Disease Modification Analysis can be applied to muscle diseases with prospectively collected muscle strength data, and a variety of rare and slowly progressive diseases. [ABSTRACT FROM AUTHOR]

Published
2019
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10. Evidence that rab27a mutations are associated with neurological involvement, not simply the hemophagocytic syndrome, in patients with Griscelli syndrome

Author

Fitzpatrick, D.L., Huizing, M., Anikster, Y., Hurvitz, H., Klar, A., Gross-Kieselstein, E., and Gahl, W.A.

Subjects
Genetic disorders -- Research, Human chromosome abnormalities -- Research, Human genetics -- Research, Gene mutations -- Physiological aspects, Neurogenetics -- Research, Pigmentation disorders -- Genetic aspects, Myosin -- Genetic aspects, Immunity -- Abnormalities, Biological sciences
Published
2001

17. Alkaptonuria: New studies of an old disease

Author

Introne, W.J., Rausche, M., Anikster, Y., Gilbert, F., and Gahl, W.A.

Subjects
Genetic research -- Analysis, Human genetics -- Research, Genetic disorders -- Research, Biological sciences
Published
2000

20. Mitochondrial epileptic encephalopathy, 3-methylglutaconic aciduria and variable complex V deficiency associated with TIMM50 mutations.

Author

Shahrour, M.A., Staretz‐Chacham, O., Dayan, D., Stephen, J., Weech, A., Damseh, N., Pri Chen, H., Edvardson, S., Mazaheri, S., Saada, A., Hershkovitz, E., Shaag, A., Huizing, M., Abu‐Libdeh, B., Gahl, W.A, Azem, A., Anikster, Y., Vilboux, T., Elpeleg, O., and Malicdan, M.C.

Subjects
MITOCHONDRIA, PEOPLE with epilepsy, HEPATIC encephalopathy, INTELLECTUAL disabilities, GENETIC mutation
Abstract

Mitochondrial encephalopathies are a heterogeneous group of disorders that, usually carry grave prognosis. Recently a homozygous mutation, Gly372Ser, in the TIMM50 gene, was reported in an abstract form, in three sibs who suffered from intractable epilepsy and developmental delay accompanied by 3-methylglutaconic aciduria. We now report on four patients from two unrelated families who presented with severe intellectual disability and seizure disorder, accompanied by slightly elevated lactate level, 3-methylglutaconic aciduria and variable deficiency of mitochondrial complex V. Using exome analysis we identified two homozygous missense mutations, Arg217Trp and Thr252Met, in the TIMM50 gene. The TIMM50 protein is a subunit of TIM23 complex, the mitochondrial import machinery. It serves as the major receptor in the intermembrane space, binding to proteins which cross the mitochondrial inner membrane on their way to the matrix. The mutations, which affected evolutionary conserved residues and segregated with the disease in the families, were neither present in large cohorts of control exome analyses nor in our ethnic specific exome cohort. Given the phenotypic similarity, we conclude that missense mutations in TIMM50 are likely manifesting by severe intellectual disability and epilepsy accompanied by 3-methylglutaconic aciduria and variable mitochondrial complex V deficiency. 3-methylglutaconic aciduria is emerging as an important biomarker for mitochondrial dysfunction, in particular for mitochondrial membrane defects. [ABSTRACT FROM AUTHOR]

Published
2017
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