LAMA2 Nonsense Variant in an Italian Greyhound with Congenital Muscular Dystrophy
A 4-month-old, male Italian Greyhound with clinical signs of a neuromuscular disease was investigated. The affected dog presented with an abnormal short-strided gait, generalized muscle atrophy, and poor growth since 2-months of age. Serum biochemistry revealed a marked elevation in creatine kinase...
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ftmdpi:oai:mdpi.com:/2073-4425/12/11/1823/ 2023-08-20T04:05:48+02:00 LAMA2 Nonsense Variant in an Italian Greyhound with Congenital Muscular Dystrophy Matthias Christen Victoria Indzhova Ling T. Guo Vidhya Jagannathan Tosso Leeb G. Diane Shelton Josep Brocal agris 2021-11-19 application/pdf https://doi.org/10.3390/genes12111823 EN eng Multidisciplinary Digital Publishing Institute Animal Genetics and Genomics https://dx.doi.org/10.3390/genes12111823 https://creativecommons.org/licenses/by/4.0/ Genes; Volume 12; Issue 11; Pages: 1823 Canis lupus familiaris dog muscle neuromuscular disease laminin merosin precision medicine animal model Text 2021 ftmdpi https://doi.org/10.3390/genes12111823 2023-08-01T03:18:25Z A 4-month-old, male Italian Greyhound with clinical signs of a neuromuscular disease was investigated. The affected dog presented with an abnormal short-strided gait, generalized muscle atrophy, and poor growth since 2-months of age. Serum biochemistry revealed a marked elevation in creatine kinase activity. Electrodiagnostic testing supported a myopathy. Histopathology of muscle biopsies confirmed a dystrophic phenotype with excessive variability in myofiber size, degenerating fibers, and endomysial fibrosis. A heritable form of congenital muscular dystrophy (CMD) was suspected, and a genetic analysis initiated. We sequenced the genome of the affected dog and compared the data to that of 795 control genomes. This search revealed a private homozygous nonsense variant in LAMA2, XM_022419950.1:c.3285G>A, predicted to truncate 65% of the open reading frame of the wild type laminin α2 protein, XP_022275658.1:p.(Trp1095*). Immunofluorescent staining performed on muscle cryosections from the affected dog confirmed the complete absence of laminin α2 in skeletal muscle. LAMA2 loss of function variants were shown to cause severe laminin α2-related CMD in humans, mouse models, and in one previously described dog. Our data together with current knowledge on other species suggest the LAMA2 nonsense variant as cause for the CMD phenotype in the investigated dog. Text Canis lupus MDPI Open Access Publishing Genes 12 11 1823 |
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Canis lupus familiaris dog muscle neuromuscular disease laminin merosin precision medicine animal model |
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Canis lupus familiaris dog muscle neuromuscular disease laminin merosin precision medicine animal model Matthias Christen Victoria Indzhova Ling T. Guo Vidhya Jagannathan Tosso Leeb G. Diane Shelton Josep Brocal LAMA2 Nonsense Variant in an Italian Greyhound with Congenital Muscular Dystrophy |
topic_facet |
Canis lupus familiaris dog muscle neuromuscular disease laminin merosin precision medicine animal model |
description |
A 4-month-old, male Italian Greyhound with clinical signs of a neuromuscular disease was investigated. The affected dog presented with an abnormal short-strided gait, generalized muscle atrophy, and poor growth since 2-months of age. Serum biochemistry revealed a marked elevation in creatine kinase activity. Electrodiagnostic testing supported a myopathy. Histopathology of muscle biopsies confirmed a dystrophic phenotype with excessive variability in myofiber size, degenerating fibers, and endomysial fibrosis. A heritable form of congenital muscular dystrophy (CMD) was suspected, and a genetic analysis initiated. We sequenced the genome of the affected dog and compared the data to that of 795 control genomes. This search revealed a private homozygous nonsense variant in LAMA2, XM_022419950.1:c.3285G>A, predicted to truncate 65% of the open reading frame of the wild type laminin α2 protein, XP_022275658.1:p.(Trp1095*). Immunofluorescent staining performed on muscle cryosections from the affected dog confirmed the complete absence of laminin α2 in skeletal muscle. LAMA2 loss of function variants were shown to cause severe laminin α2-related CMD in humans, mouse models, and in one previously described dog. Our data together with current knowledge on other species suggest the LAMA2 nonsense variant as cause for the CMD phenotype in the investigated dog. |
format |
Text |
author |
Matthias Christen Victoria Indzhova Ling T. Guo Vidhya Jagannathan Tosso Leeb G. Diane Shelton Josep Brocal |
author_facet |
Matthias Christen Victoria Indzhova Ling T. Guo Vidhya Jagannathan Tosso Leeb G. Diane Shelton Josep Brocal |
author_sort |
Matthias Christen |
title |
LAMA2 Nonsense Variant in an Italian Greyhound with Congenital Muscular Dystrophy |
title_short |
LAMA2 Nonsense Variant in an Italian Greyhound with Congenital Muscular Dystrophy |
title_full |
LAMA2 Nonsense Variant in an Italian Greyhound with Congenital Muscular Dystrophy |
title_fullStr |
LAMA2 Nonsense Variant in an Italian Greyhound with Congenital Muscular Dystrophy |
title_full_unstemmed |
LAMA2 Nonsense Variant in an Italian Greyhound with Congenital Muscular Dystrophy |
title_sort |
lama2 nonsense variant in an italian greyhound with congenital muscular dystrophy |
publisher |
Multidisciplinary Digital Publishing Institute |
publishDate |
2021 |
url |
https://doi.org/10.3390/genes12111823 |
op_coverage |
agris |
genre |
Canis lupus |
genre_facet |
Canis lupus |
op_source |
Genes; Volume 12; Issue 11; Pages: 1823 |
op_relation |
Animal Genetics and Genomics https://dx.doi.org/10.3390/genes12111823 |
op_rights |
https://creativecommons.org/licenses/by/4.0/ |
op_doi |
https://doi.org/10.3390/genes12111823 |
container_title |
Genes |
container_volume |
12 |
container_issue |
11 |
container_start_page |
1823 |
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1774716531915096064 |