The integration of next-generation sequencing (NGS) technologies into routine genetic diagnostics and the ensuing yield of novel disease genes has greatly expanded the number of loci associated with axonal neuropathies. 2, 3, 4 This variability not only results in complex phenotypic categorizations but also in diagnostic challenges and potential misinterpretation of genetic findings. Clinically, HMNs/CMT2 present with extreme heterogeneity in terms of onset, clinical course, associated neurological features (i.e., sensory or cerebellar involvement), and other co-presenting signs, including seizures, fractures, and respiratory distress, among others. 1 The cardinal phenotype of these entities is a length-dependent motor neuropathy that predominantly affects the distal foot and peroneal muscles and results in foot abnormalities or deformities and gait disturbance. The distal hereditary motor neuropathies (HMNs) are characterized by pure motor neuropathy, whereas the axonal Charcot-Marie-Tooth neuropathy (CMT2) have both motor and sensory involvement. 1 Classically, they are classified into two subgroups depending on the affected fiber type. Hereditary axonal neuropathies are a heterogenous group of disorders characterized by normal or moderately reduced nerve conduction velocities. Our results not only reinforce the existing link between Golgi fragmentation and neurodegeneration but also demonstrate that pathogenic variants in GBF1 are associated with HMN/CMT2. Consistent with the described role of GBF1 in Golgi function and maintenance, we observed marked increase in Golgi fragmentation in primary fibroblasts derived from all affected individuals in this study. We demonstrate that GBF1 is present in mouse spinal cord and muscle tissues and is particularly abundant in neuropathologically relevant sites, such as the motor neuron and the growth cone. GBF1 is mainly involved in the formation of coatomer protein complex (COPI) vesicles, maintenance and function of the Golgi apparatus, and mitochondria migration and positioning. GBF1 encodes a guanine-nucleotide exchange factor that facilitates the activation of members of the ARF (ADP-ribosylation factor) family of small GTPases. Three individuals had additional distal sensory loss. Electrophysiological studies confirmed axonal damage with chronic neurogenic changes. Affected individuals show HMN/CMT2 with slowly progressive distal muscle weakness and musculoskeletal deformities.

Other known HMN/CMT2-implicated genes were excluded.

Genomic sequencing analyses in seven affected individuals uncovered four distinct heterozygous GBF1 variants, two of which occurred de novo. Here, we report the identification of pathogenic variants in GBF1 (Golgi brefeldin A-resistant guanine nucleotide exchange factor 1) in four unrelated families with individuals affected by sporadic or dominant HMN/CMT2. The genetic cause for about half of the individuals affected by HMN/CMT2 remains unknown. And in an IG Story, she posted a photo of herself completely in the nude.Distal hereditary motor neuropathies (HMNs) and axonal Charcot-Marie-Tooth neuropathy (CMT2) are clinically and genetically heterogeneous diseases characterized primarily by motor neuron degeneration and distal weakness. In the final one, Olivia is freeing the nipple in a wet white T-shirt. In another, she’s facing away from the camera in high-waisted briefs while showing off super-toned legs. In one shot, the actress faces the camera with her hands over her head and censor bars over her bare breasts. Olivia posted a few pics of herself posing totally naked (and in her underwear) from the campaign-and they’re everything. And she shows it off in a brand new ad campaign for the natural and organic line, True Botanicals.

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