Novel missense mutation and large deletion of <i>GNE</i> gene in autosomal‐recessive inclusion‐body myopathy

Bo, Roberto Del; Baron, Pierluigi; Prelle, A.; Serafini, Massimo; Moggio, Maurizio; Fonzo, Alessio Di; Castagni, M.; Bresolin, Nereo; Comi, Giacomo P.

doi:10.1002/mus.10391

Cited by 32 publications

(8 citation statements)

References 10 publications

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“…Patients with typical clinical and histological manifestations and only one heterozygous GNE mutation identified by sequencing have been encountered. Such patients may have deletions25 not identified by sequencing or mutations in non-coding regions of GNE on the other allele. Alternatively, they may have a genetically different disorder.…”

Section: Diagnosismentioning

confidence: 99%

GNE myopathy: current update and future therapy

Nishino

Carrillo-Carrasco

Argov

2014

J Neurol Neurosurg Psychiatry

138

126

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Section: Diagnosismentioning

confidence: 99%

GNE myopathy: current update and future therapy

Nishino

Carrillo-Carrasco

Argov

2014

J Neurol Neurosurg Psychiatry

138

126

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“…Table S1). The additional three indels are larger insertions or deletions for which the exact sequence data were not provided and/or not retrievable, including insertion of 10‐bp in exon 3 [Nishino et al., ], exon 3 deletion [Cho et al., ], and a large (>35.7 kb) deletion spanning exons 2–10 [Del Bo et al., ]. Because these three variants delete large regions of GNE and/or are out of frame and likely resulting in an early termination codon and/or nonsense‐mediated decay, we assigned them as “severe.”…”

Section: Functional Prediction Of Variantsmentioning

confidence: 99%

Mutation Update forGNEGene Variants Associated with GNE Myopathy

et al. 2014

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The GNE gene encodes the rate-limiting, bifunctional enzyme of sialic acid biosynthesis, UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase (GNE). Biallelic GNE mutations underlie GNE myopathy, an adult-onset progressive myopathy. GNE myopathy-associated GNE mutations are predominantly missense, resulting in reduced, but not absent, GNE enzyme activities. The exact pathomechanism of GNE myopathy remains unknown, but likely involves aberrant (muscle) sialylation. Here we summarize 154 reported and novel GNE variants associated with GNE myopathy, including 122 missense, 11 nonsense, 14 insertion/deletions and 7 intronic variants. All variants were deposited in the online GNE variation database (http://www.dmd.nl/nmdb2/home.php?select_db=GNE). We report the predicted effects on protein function of all variants as well as the predicted effects on epimerase and/or kinase enzymatic activities of selected variants. By analyzing exome sequence databases, we identified three frequently occurring, unreported GNE missense variants/polymorphisms, important for future sequence interpretations. Based on allele frequencies, we estimate the world-wide prevalence of GNE myopathy to be ~ 4–21/1,000,000. This previously unrecognized high prevalence confirms suspicions that many patients may escape diagnosis. Awareness among physicians for GNE myopathy is essential for the identification of new patients, which is required for better understanding of the disorder’s pathomechanism and for the success of ongoing treatment trials.

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“…Similar to h‐IBM Middle Eastern patients, strong linkage disequilibrium has also been demonstrated in Japanese patients with DMRV who carry the homozygous missense mutation p.V572L 5. To date, more than 50 different mutations (including point mutations, deletions, and small insertions) of the GNE gene have been identified in h‐IBM/DMRV patients worldwide 6–17…”

mentioning

confidence: 94%

Hereditary inclusion‐body myopathy: Clues on pathogenesis and possible therapy

Broccolini

Gidaro²,

Morosetti

et al. 2009

Muscle and Nerve

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Hereditary inclusion-body myopathy (h-IBM), or distal myopathy with rimmed vacuoles (DMRV), is an autosomal recessive disorder with onset in early adult life and a progressive course leading to severe disability. h-IBM/DMRV is due to mutations of a gene (GNE) that codes for a rate-limiting enzyme in the sialic acid biosynthetic pathway. Despite the identification of the causative gene defect, it has not been unambiguously clarified how GNE gene mutations impair muscle metabolism. Although numerous studies have indicated a key role of hyposialylation of glycoproteins in h-IBM/DMRV pathogenesis, others have demonstrated new and unpredicted functions of the GNE gene, outside the sialic acid biosynthetic pathway, that may also be relevant. This review illustrates the clinical and pathologic characteristics of h-IBM/DMRV and the main clues available to date concerning the possible pathogenic mechanisms and therapeutic perspectives of this disorder.

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Novel missense mutation and large deletion of GNE gene in autosomal‐recessive inclusion‐body myopathy

Cited by 32 publications

References 10 publications

GNE myopathy: current update and future therapy

GNE myopathy: current update and future therapy

Mutation Update forGNEGene Variants Associated with GNE Myopathy

Hereditary inclusion‐body myopathy: Clues on pathogenesis and possible therapy

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