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Case report: Adult-onset limb girdle muscular dystrophy in sibling pair due to novel homozygous LAMA2 missense variant

Recessive pathogenic variants in the laminin subunit alpha 2 (LAMA2) gene cause a spectrum of disease ranging from severe congenital muscular dystrophy to later-onset limb girdle muscular dystrophy (LGMDR23). The phenotype of LGMDR23 is characterized by slowly progressive proximal limb weakness, con...

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Autores principales: Katz, Matthew, Waddell, Leigh B., Yuen, Michaela, Bryen, Samantha J., Oates, Emily, Garton, Fleur C., Robertson, Thomas, Henderson, Robert David, Cooper, Sandra T., McCombe, Pamela A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9911805/
https://www.ncbi.nlm.nih.gov/pubmed/36779065
http://dx.doi.org/10.3389/fneur.2023.1055639
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author Katz, Matthew
Waddell, Leigh B.
Yuen, Michaela
Bryen, Samantha J.
Oates, Emily
Garton, Fleur C.
Robertson, Thomas
Henderson, Robert David
Cooper, Sandra T.
McCombe, Pamela A.
author_facet Katz, Matthew
Waddell, Leigh B.
Yuen, Michaela
Bryen, Samantha J.
Oates, Emily
Garton, Fleur C.
Robertson, Thomas
Henderson, Robert David
Cooper, Sandra T.
McCombe, Pamela A.
author_sort Katz, Matthew
collection PubMed
description Recessive pathogenic variants in the laminin subunit alpha 2 (LAMA2) gene cause a spectrum of disease ranging from severe congenital muscular dystrophy to later-onset limb girdle muscular dystrophy (LGMDR23). The phenotype of LGMDR23 is characterized by slowly progressive proximal limb weakness, contractures, raised creatine kinase, and sometimes distinctive cerebral white matter changes and/or epilepsy. We present two siblings, born to consanguineous parents, who developed adult-onset LGMDR23 associated with typical cerebral white matter changes and who both later developed dementia. The male proband also had epilepsy and upper motor neuron signs when he presented at age 72. Merosin immunohistochemistry and Western blot on muscle biopsies taken from both subjects was normal. Whole exome sequencing revealed a previously unreported homozygous missense variant in LAMA2 [Chr6(GRCh38):g.129297734G>A; NM_000426.3:c.2906G>A; p.(Cys969Tyr)] in the proband. The same homozygous LAMA2 variant was confirmed by Sanger sequencing in the proband's affected sister. These findings expand the genotypic and phenotypic spectrum of LGMDR23.
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spelling pubmed-99118052023-02-11 Case report: Adult-onset limb girdle muscular dystrophy in sibling pair due to novel homozygous LAMA2 missense variant Katz, Matthew Waddell, Leigh B. Yuen, Michaela Bryen, Samantha J. Oates, Emily Garton, Fleur C. Robertson, Thomas Henderson, Robert David Cooper, Sandra T. McCombe, Pamela A. Front Neurol Neurology Recessive pathogenic variants in the laminin subunit alpha 2 (LAMA2) gene cause a spectrum of disease ranging from severe congenital muscular dystrophy to later-onset limb girdle muscular dystrophy (LGMDR23). The phenotype of LGMDR23 is characterized by slowly progressive proximal limb weakness, contractures, raised creatine kinase, and sometimes distinctive cerebral white matter changes and/or epilepsy. We present two siblings, born to consanguineous parents, who developed adult-onset LGMDR23 associated with typical cerebral white matter changes and who both later developed dementia. The male proband also had epilepsy and upper motor neuron signs when he presented at age 72. Merosin immunohistochemistry and Western blot on muscle biopsies taken from both subjects was normal. Whole exome sequencing revealed a previously unreported homozygous missense variant in LAMA2 [Chr6(GRCh38):g.129297734G>A; NM_000426.3:c.2906G>A; p.(Cys969Tyr)] in the proband. The same homozygous LAMA2 variant was confirmed by Sanger sequencing in the proband's affected sister. These findings expand the genotypic and phenotypic spectrum of LGMDR23. Frontiers Media S.A. 2023-01-27 /pmc/articles/PMC9911805/ /pubmed/36779065 http://dx.doi.org/10.3389/fneur.2023.1055639 Text en Copyright © 2023 Katz, Waddell, Yuen, Bryen, Oates, Garton, Robertson, Henderson, Cooper and McCombe. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Neurology
Katz, Matthew
Waddell, Leigh B.
Yuen, Michaela
Bryen, Samantha J.
Oates, Emily
Garton, Fleur C.
Robertson, Thomas
Henderson, Robert David
Cooper, Sandra T.
McCombe, Pamela A.
Case report: Adult-onset limb girdle muscular dystrophy in sibling pair due to novel homozygous LAMA2 missense variant
title Case report: Adult-onset limb girdle muscular dystrophy in sibling pair due to novel homozygous LAMA2 missense variant
title_full Case report: Adult-onset limb girdle muscular dystrophy in sibling pair due to novel homozygous LAMA2 missense variant
title_fullStr Case report: Adult-onset limb girdle muscular dystrophy in sibling pair due to novel homozygous LAMA2 missense variant
title_full_unstemmed Case report: Adult-onset limb girdle muscular dystrophy in sibling pair due to novel homozygous LAMA2 missense variant
title_short Case report: Adult-onset limb girdle muscular dystrophy in sibling pair due to novel homozygous LAMA2 missense variant
title_sort case report: adult-onset limb girdle muscular dystrophy in sibling pair due to novel homozygous lama2 missense variant
topic Neurology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9911805/
https://www.ncbi.nlm.nih.gov/pubmed/36779065
http://dx.doi.org/10.3389/fneur.2023.1055639
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