A Novel&lt;b&gt; &lt;/b&gt;Mutation of the &lt;b&gt;&lt;i&gt;GNE&lt;/i&gt;&lt;/b&gt; Gene in Distal Myopathy with Rimmed Vacuoles: A Case with Inflammation

Tanboon, Jantima; Rongsa, Kanjana; Pithukpakorn, Manop; Boonyapisit, Kanokwan; Limwongse, Chanin; Sangruchi, Tumtip

doi:10.1159/000360730

Cited by 6 publications

(2 citation statements)

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“…Other hallmarks of GNEM are the finding of rimmed vacuoles in affected muscles [ 60 , 63 ], an onset in early adulthood [ 62 , 64 ], and a quite slow progression of the disease [ 8 , 65 ]. GNEM-triggered inflammatory changes are not typical features of this disease [ 60 , 63 , 66 ], although there are confirmed exceptions to this statement [ 67 , 68 , 69 ].…”

Section: Introductionmentioning

confidence: 99%

Glycation Interferes with the Activity of the Bi-Functional UDP-N-Acetylglucosamine 2-Epimerase/N-Acetyl-mannosamine Kinase (GNE)

et al. 2023

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Mutations in the gene coding for the bi-functional UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase (GNE), the key enzyme of the sialic acid biosynthesis, are responsible for autosomal-recessive GNE myopathy (GNEM). GNEM is an adult-onset disease with a yet unknown exact pathophysiology. Since the protein appears to work adequately for a certain period of time even though the mutation is already present, other effects appear to influence the onset and progression of the disease. In this study, we want to investigate whether the late onset of GNEM is based on an age-related effect, e.g., the accumulation of post-translational modifications (PTMs). Furthermore, we also want to investigate what effect on the enzyme activity such an accumulation would have. We will particularly focus on glycation, which is a PTM through non-enzymatic reactions between the carbonyl groups (e.g., of methylglyoxal (MGO) or glyoxal (GO)) with amino groups of proteins or other biomolecules. It is already known that the levels of both MGO and GO increase with age. For our investigations, we express each domain of the GNE separately, treat them with one of the glycation agents, and determine their activity. We demonstrate that the enzymatic activity of the N-acetylmannosamine kinase (GNE-kinase domain) decreases dramatically after glycation with MGO or GO—with a remaining activity of 13% ± 5% (5 mM MGO) and 22% ± 4% (5 mM GO). Whereas the activity of the UDP-N-acetylglucosamine 2-epimerase (GNE-epimerase domain) is only slightly reduced after glycation—with a remaining activity of 60% ± 8% (5 mM MGO) and 63% ± 5% (5 mM GO).

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Section: Introductionmentioning

confidence: 99%

Glycation Interferes with the Activity of the Bi-Functional UDP-N-Acetylglucosamine 2-Epimerase/N-Acetyl-mannosamine Kinase (GNE)

et al. 2023

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“…This disorder was initially described as a distal myopathy in Japanese [ 3 ], and as a quadriceps sparing myopathy in Iranian Jews [ 4 ], associated with rimmed vacuoles on muscle biopsy. However, the phenotype and histopathological features seem to be more heterogeneous than initially expected, as limb-girdle presentation [ 5 ] as well as cases with histological inflammation [ 6, 7 ] or without rimmed vacuoles [ 8 ] associated to GNE myopathy have been reported.…”

Section: Introductionmentioning

confidence: 99%

Novel Pathogenic Variants in a French Cohort Widen the Mutational Spectrum of GNE Myopathy

Cerino

Gorokhova

Béhin

et al. 2015

JND

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Background: GNE myopathy is a rare autosomal recessively inherited muscle disease resulting from mutations in the gene encoding GNE (UDP-N-acetylglucosamine-2-epimerase/N-acetylmannosamine kinase), a key enzyme in sialic acid biosynthesis. 154 different pathogenic variants have been previously associated with GNE myopathy.Objective: Describe novel pathogenic variants associated with GNE myopathy in a large French cohort.Methods: We analyzed mutational data from 32 GNE myopathy index patients. Novel, as well as previously published pathogenic variants, were examined for possible deleterious effects on splicing.Results: We describe 13 novel pathogenic variants in GNE, identified in the first large French cohort reported to date. We also find that 6 published pathogenic variants might have a previously unrecognized deleterious effect on splicing.Conclusions: Novel pathogenic GNE variants described here raise the total number of different pathogenic variants reported to 167, complementing the recently published GNE mutation update. Our novel findings on possible splice-disrupting effects by several variants suggest that the pathogenicity mechanism of these variants could be reinterpreted, expanding our knowledge about the GNE mutational spectrum.

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Gene analysis and clinical features of 22 GNE myopathy patients

et al. 2022

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A Novel<b> </b>Mutation of the <b><i>GNE</i></b> Gene in Distal Myopathy with Rimmed Vacuoles: A Case with Inflammation

Cited by 6 publications

References 13 publications

Glycation Interferes with the Activity of the Bi-Functional UDP-N-Acetylglucosamine 2-Epimerase/N-Acetyl-mannosamine Kinase (GNE)

Glycation Interferes with the Activity of the Bi-Functional UDP-N-Acetylglucosamine 2-Epimerase/N-Acetyl-mannosamine Kinase (GNE)

Novel Pathogenic Variants in a French Cohort Widen the Mutational Spectrum of GNE Myopathy

Gene analysis and clinical features of 22 GNE myopathy patients

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