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Bialelic Pathogenic (c.830G>A(p.R277Q)) Variant Disrupting the GNE Gene Function and Causes Nonaka myopathy Phenotype

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Abstract

Nonaka myopathy (MIM 605820) is caused by homozygous pathogenic variants in the GNE gene. It is a recessively inherited early adult-onset myopathy that usually preserves the quadriceps and presents with bilateral foot drop, usually caused by anterior tibialis weakness. In patients with Nonaka myopathy, serum creatine kinases are slightly elevated, muscle weakness progresses slowly, and ambulation loss develops after 15–20 yr. The current study aims to raise awareness of Nonaka myopathy that occurs as a rare phenotype due to pathogenic variants in GNE gene. Detailed family histories and clinical data were recorded. Whole exome sequencing was performed and co-segregation analysis of the family were done by Sanger sequencing. Also the homology model of the mutant protein was created with the ProMod3 algorithm. We identified a bialelic pathogenic variant (c.830G>A) in GNE gene, which explain the patients' clinical status. We present the main findings of two siblings with Nonaka myopathy together with detailed clinical and genetic profiles of the patients together with a three-dimensional mutant GNE protein model. We think that the clinical characteristics and the effect of the (c.830G>A) variant will facilitate our understanding of GNE gene in Nonaka myopathy pathogenesis.

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Authors and Affiliations

  1. Department of Medical Genetics, Basaksehir Cam and Sakura City Hospital, 34480, Istanbul, Turkey

    Mustafa Doğan & Alper Gezdirici

  2. Department of Bioengineering, Malatya Turgut Ozal University, 44200, Malatya, Turkey

    Ekrem Akbulut

  3. Duzce University Medical Faculty, Department of Medical Genetics, 81620, Duzce, Turkey

    Recep Eroz

  4. Cukurova University Medical Faculty, Department of Medical Genetics, 81620, Adana, Turkey

    Sevcan Tuğ Bozdoğan

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  1. Mustafa Doğan
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Correspondence to Mustafa Doğan.

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Statement of compliance with standards of research involving humans as subjects. We alone are responsible for the content and writing of this article. We thank the patients for their participation in our study. Written informed consents for medical examinations, genomic analyses and case presentations were obtained from all participants and human specimen were collected in accordance with the criteria of the Declaration of Helsinki.

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Doğan, M., Akbulut, E., Gezdirici, A. et al. Bialelic Pathogenic (c.830G>A(p.R277Q)) Variant Disrupting the GNE Gene Function and Causes Nonaka myopathy Phenotype. Cytol. Genet. 57, 347–355 (2023). https://doi.org/10.3103/S0095452723040035

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