A novel <i>BICD2</i> mutation of a patient with Spinal Muscular Atrophy Lower Extremity Predominant 2

DOI Web Site 参考文献29件 オープンアクセス
  • Tumurkhuu Munkhtuya
    Department of Molecular Biology, International University of Health and Welfare, School of Medicine, Narita, Chiba, Japan. Department of Genetics and Molecular Biology, School of Bio-Medicine, Mongolian National University of Medical Sciences, Mongolia.
  • Batbuyan Uranchimeg
    Department of Genetics and Molecular Biology, School of Bio-Medicine, Mongolian National University of Medical Sciences, Mongolia.
  • Yuzawa Satoru
    Department of Biochemistry, International University of Health and Welfare, School of Medicine, Narita, Chiba, Japan.
  • Munkhsaikhan Yanjinlkham
    Department of Genetics and Molecular Biology, School of Bio-Medicine, Mongolian National University of Medical Sciences, Mongolia.
  • Batmunkh Ganbayar
    Laboratory of Medical Genetics, National Center of Maternal and Child Health, Mongolia.
  • Nishimura Wataru
    Department of Molecular Biology, International University of Health and Welfare, School of Medicine, Narita, Chiba, Japan.

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<p>The bicaudal D homolog 2 (BICD2) gene encodes a protein required for the stable complex of dynein and dynactin, which functions as a motor protein working along the microtubule cytoskeleton. Both inherited and de novo variants of BICD2 are reported with autosomal dominant spinal muscular atrophy with lower extremity predominance (SMALED2). Here, we report a male patient with a novel mutation in the BICD2 gene caused by a heterozygous substitution of arginine with cysteine at residue 162 (Arg162Cys); inherited from his asymptomatic mother. The patient showed typical clinical symptoms of SMALED2, which was genetically confirmed by sequencing. The Arg162Cys mutant clusters with four previously reported variants (c.361C>G, p.Leu121Val; c.581A>G, p.Gln194Arg; c.320C>T, p.Ser107Leu; c.565A>T, p.Ile189Phe) in a region that binds to the dynein-dynactin complex (DDC). The BICD2 domain structures were predicted and the Arg162Cys mutation was localized in the N-terminus coiled-coil segment 1 (CC1) domain. Protein modeling of BICD2's CC1 domain predicted that the Arg162Cys missense variant disrupted interactions with dynein cytoplasmic 1 heavy chain 1 within the DDC. The mutant did this by either changing the electrostatic surface potential or making a broader hydrophobic unit with the neighboring residues. This hereditary case supports the complex and broad genotype-phenotype correlation of BICD2 mutations, which could be explained by incomplete penetrance or variable expressivity in the next generation. </p>

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  • Intractable & Rare Diseases Research

    Intractable & Rare Diseases Research 10 (2), 102-108, 2021-05-31

    特定非営利活動法人 バイオ＆ソーシャル・サイエンス推進国際研究交流会

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