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A Novel CAPN1 Mutation Causes a Pure Hereditary Spastic Paraplegia in an Italian Family.

Abstract

CAPN1 encodes calpain-1, a large subunit of μ-calpain, a calcium-activated cysteine protease widely present in the central nervous system. Mutations in CAPN1 have recently been identified in a complicated form of Hereditary Spastic Paraplegia (HSP) with a combination of cerebellar ataxia and corticomotor tract disorder (SPG76). Therefore, CAPN1 is now considered one of those genes that clinically manifest with a spectrum of disorders ranging from spasticity to cerebellar ataxia and represent a link between Spinocerebellar Ataxia and HSP, two groups of diseases previously considered separate but sharing pathophysiological pathways. We here describe clinical and molecular findings of two Italian adult siblings affected with a pure form of HSP and harboring the novel homozygote c.959delA variant (p.Tyr320Leufs*73) in the CAPN1 gene. Although the reason why mutations in CAPN1 may cause heterogeneous clinical pictures remains speculative, our findings confirm that the spectrum of the CAPN1-linked phenotypes includes pure HSP with onset during the third decade of life. Further studies are warrantied in order to clarify the mechanism underlying the differences in CAPN1 mutation clinical expression.

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  • Authors+Show Affiliations

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    Unit of Neurology, Center for Neuromuscular Diseases, ASST Spedali Civili and University of Brescia, Brescia, Italy.

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    Laboratory of Molecular Biology, Scientific Institute IRCCS E. Medea, Lecco, Italy.

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    Laboratory of Molecular Biology, Scientific Institute IRCCS E. Medea, Lecco, Italy.

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    Department of Neurosciences, Reproductive Sciences and Odontostomatology, University Federico II of Naples, Naples, Italy.

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    Department of Neurosciences, Reproductive Sciences and Odontostomatology, University Federico II of Naples, Naples, Italy.

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    Unit of Molecular Medicine, IRCCS Foundation Stella Maris, Pisa, Italy.

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    Unit of Neurology, Center for Neuromuscular Diseases, ASST Spedali Civili and University of Brescia, Brescia, Italy.

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    Unit of Neurology, Center for Neuromuscular Diseases, ASST Spedali Civili and University of Brescia, Brescia, Italy.

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    Unit of Neurology, Center for Neuromuscular Diseases, ASST Spedali Civili and University of Brescia, Brescia, Italy.

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    Unit of Neurology, Center for Neuromuscular Diseases, ASST Spedali Civili and University of Brescia, Brescia, Italy.

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    Department of Neurosciences, Reproductive Sciences and Odontostomatology, University Federico II of Naples, Naples, Italy.

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    Unit of Neurology, Center for Neuromuscular Diseases, ASST Spedali Civili and University of Brescia, Brescia, Italy.

    Unit of Neurology, Center for Neuromuscular Diseases, ASST Spedali Civili and University of Brescia, Brescia, Italy.

    Source

    Frontiers in neurology 10: 2019 pg 580

    Pub Type(s)

    Case Reports

    Language

    eng

    PubMed ID

    31231303

    Citation

    Cotti Piccinelli, Stefano, et al. "A Novel CAPN1 Mutation Causes a Pure Hereditary Spastic Paraplegia in an Italian Family." Frontiers in Neurology, vol. 10, 2019, p. 580.
    Cotti Piccinelli S, Bassi MT, Citterio A, et al. A Novel CAPN1 Mutation Causes a Pure Hereditary Spastic Paraplegia in an Italian Family. Front Neurol. 2019;10:580.
    Cotti Piccinelli, S., Bassi, M. T., Citterio, A., Manganelli, F., Tozza, S., Santorelli, F. M., ... Filosto, M. (2019). A Novel CAPN1 Mutation Causes a Pure Hereditary Spastic Paraplegia in an Italian Family. Frontiers in Neurology, 10, p. 580. doi:10.3389/fneur.2019.00580.
    Cotti Piccinelli S, et al. A Novel CAPN1 Mutation Causes a Pure Hereditary Spastic Paraplegia in an Italian Family. Front Neurol. 2019;10:580. PubMed PMID: 31231303.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - A Novel CAPN1 Mutation Causes a Pure Hereditary Spastic Paraplegia in an Italian Family. AU - Cotti Piccinelli,Stefano, AU - Bassi,Maria T, AU - Citterio,Andrea, AU - Manganelli,Fiore, AU - Tozza,Stefano, AU - Santorelli,Filippo M, AU - Gallo Cassarino,Serena, AU - Caria,Filomena, AU - Baldelli,Enrico, AU - Galvagni,Anna, AU - Santoro,Lucio, AU - Padovani,Alessandro, AU - Filosto,Massimiliano, Y1 - 2019/06/05/ PY - 2019/03/08/received PY - 2019/05/16/accepted PY - 2019/6/25/entrez PY - 2019/6/25/pubmed PY - 2019/6/25/medline KW - CAPN1 KW - HSP KW - SCA KW - ataxia KW - calpain-1 KW - hereditary spastic paraplegia KW - spinocerebellar ataxia SP - 580 EP - 580 JF - Frontiers in neurology JO - Front Neurol VL - 10 N2 - CAPN1 encodes calpain-1, a large subunit of μ-calpain, a calcium-activated cysteine protease widely present in the central nervous system. Mutations in CAPN1 have recently been identified in a complicated form of Hereditary Spastic Paraplegia (HSP) with a combination of cerebellar ataxia and corticomotor tract disorder (SPG76). Therefore, CAPN1 is now considered one of those genes that clinically manifest with a spectrum of disorders ranging from spasticity to cerebellar ataxia and represent a link between Spinocerebellar Ataxia and HSP, two groups of diseases previously considered separate but sharing pathophysiological pathways. We here describe clinical and molecular findings of two Italian adult siblings affected with a pure form of HSP and harboring the novel homozygote c.959delA variant (p.Tyr320Leufs*73) in the CAPN1 gene. Although the reason why mutations in CAPN1 may cause heterogeneous clinical pictures remains speculative, our findings confirm that the spectrum of the CAPN1-linked phenotypes includes pure HSP with onset during the third decade of life. Further studies are warrantied in order to clarify the mechanism underlying the differences in CAPN1 mutation clinical expression. SN - 1664-2295 UR - https://www.unboundmedicine.com/medline/citation/31231303/A_Novel_CAPN1_Mutation_Causes_a_Pure_Hereditary_Spastic_Paraplegia_in_an_Italian_Family L2 - https://dx.doi.org/10.3389/fneur.2019.00580 DB - PRIME DP - Unbound Medicine ER -