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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ftdoajarticles:oai:doaj.org/article:312d178b26e94686b4736c82686b1855 2023-05-15T15:50:35+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 2021-11-01T00:00:00Z https://doi.org/10.3390/genes12111823 https://doaj.org/article/312d178b26e94686b4736c82686b1855 EN eng MDPI AG https://www.mdpi.com/2073-4425/12/11/1823 https://doaj.org/toc/2073-4425 doi:10.3390/genes12111823 2073-4425 https://doaj.org/article/312d178b26e94686b4736c82686b1855 Genes, Vol 12, Iss 1823, p 1823 (2021) Canis lupus familiaris dog muscle neuromuscular disease laminin merosin Genetics QH426-470 article 2021 ftdoajarticles https://doi.org/10.3390/genes12111823 2022-12-31T07:31:07Z 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. Article in Journal/Newspaper Canis lupus Directory of Open Access Journals: DOAJ Articles Genes 12 11 1823 |
institution |
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Directory of Open Access Journals: DOAJ Articles |
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ftdoajarticles |
language |
English |
topic |
Canis lupus familiaris dog muscle neuromuscular disease laminin merosin Genetics QH426-470 |
spellingShingle |
Canis lupus familiaris dog muscle neuromuscular disease laminin merosin Genetics QH426-470 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 Genetics QH426-470 |
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 |
Article in Journal/Newspaper |
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 |
MDPI AG |
publishDate |
2021 |
url |
https://doi.org/10.3390/genes12111823 https://doaj.org/article/312d178b26e94686b4736c82686b1855 |
genre |
Canis lupus |
genre_facet |
Canis lupus |
op_source |
Genes, Vol 12, Iss 1823, p 1823 (2021) |
op_relation |
https://www.mdpi.com/2073-4425/12/11/1823 https://doaj.org/toc/2073-4425 doi:10.3390/genes12111823 2073-4425 https://doaj.org/article/312d178b26e94686b4736c82686b1855 |
op_doi |
https://doi.org/10.3390/genes12111823 |
container_title |
Genes |
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12 |
container_issue |
11 |
container_start_page |
1823 |
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1766385569808515072 |