Histopathological proof of the pathogenicity of a rare GFAP mutation in a patient with flaccid paraparesis

Brackmann, Florian; Coras, Roland; Rössler, Karl; Kraus, Cornelia; Rompel, Oliver; Trollmann, Regina

doi:10.1016/j.braindev.2017.11.005

Cited by 2 publications

References 9 publications

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Atlas ofDES(desmin) variants: Impact of variants located within the head domain on filament assembly

Voß,

Walhorn,

Holler

et al. 2023

Preprint

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Desmin is a muscle-specific intermediate filament protein, which plays a significant role in providing structural integrity of cardiomyocytes by connecting different cell organelles and multi-protein complexes. DES mutations cause cardiomyopathies and skeletal myopathies. Most of these pathogenic mutations are localized in the highly conserved rod domain and affect the filament assembly. However, the impact of DES variants within the N-terminal head domain on the filament assembly process is widely unknown. Therefore, we inserted a set of 85 different head domain variants with unknown significance from human genetic databases in expression constructs and investigated their impact on filament formation in cell culture in combination with confocal microscopy. The majority of these desmin variants do not affect the filament assembly. However, the desmin variants -p.S13P, -p.N107D, -p.E108G and -p.K109E significantly inhibit the filament assembly. Additionally, we expressed and purified recombinant desmin and investigated the filament assembly defects by atomic force microscopy verifying these findings at the single molecular level. Furthermore, we truncated systematically the head domain to investigate which general parts of this domain are necessary for filament assembly. In summary, our functional investigations might be relevant for the classification of novel DES variants and the genetic counselling of patients carrying desmin head variants.

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Atlas ofDES(desmin) variants: Impact of variants located within the head domain on filament assembly

Voß,

Walhorn,

Holler

et al. 2023

Preprint

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Spinal Cord Involvement in Pediatric-Onset Metabolic Disorders With Mendelian and Mitochondrial Inheritance

et al. 2021

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Previous reviews have described the features of brain involvement in pediatric-onset metabolic disorders with Mendelian and mitochondrial inheritance, but only a few have focused on spinal cord abnormalities. An increasing number of metabolic disorders with Mendelian and mitochondrial inheritance in children with predominant spinal cord involvement has been recognized. Spinal cord involvement may be isolated or may occur more frequently with brain involvement. Timely diagnosis and occasional genetic counseling are needed for timely therapy. Therefore, clinicians must be aware of the clinical, laboratory, and radiographic features of these disorders. In this review, we describe pediatric-onset metabolic disorders with Mendelian and mitochondrial inheritance and predominant spinal cord involvement. Furthermore, we provide an overview of these conditions, including background information and examples that require rapid identification, focusing on treatable conditions; that would be catastrophic if they are not recognized.

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Histopathological proof of the pathogenicity of a rare GFAP mutation in a patient with flaccid paraparesis

Cited by 2 publications

References 9 publications

Atlas ofDES(desmin) variants: Impact of variants located within the head domain on filament assembly

Atlas ofDES(desmin) variants: Impact of variants located within the head domain on filament assembly

Spinal Cord Involvement in Pediatric-Onset Metabolic Disorders With Mendelian and Mitochondrial Inheritance

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