<i>LAMA2</i> 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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Autores principales:	Matthias Christen, Victoria Indzhova, Ling T. Guo, Vidhya Jagannathan, Tosso Leeb, G. Diane Shelton, Josep Brocal
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	<i>Canis lupus familiaris</i> dog muscle neuromuscular disease laminin merosin Genetics QH426-470
Acceso en línea:	https://doaj.org/article/312d178b26e94686b4736c82686b1855
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spelling	oai:doaj.org-article:312d178b26e94686b4736c82686b18552021-11-25T17:42:24Z<i>LAMA2</i> Nonsense Variant in an Italian Greyhound with Congenital Muscular Dystrophy10.3390/genes121118232073-4425https://doaj.org/article/312d178b26e94686b4736c82686b18552021-11-01T00:00:00Zhttps://www.mdpi.com/2073-4425/12/11/1823https://doaj.org/toc/2073-4425A 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 <i>LAMA2</i>, 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. <i>LAMA2</i> 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 <i>LAMA2</i> nonsense variant as cause for the CMD phenotype in the investigated dog.Matthias ChristenVictoria IndzhovaLing T. GuoVidhya JagannathanTosso LeebG. Diane SheltonJosep BrocalMDPI AGarticle<i>Canis lupus familiaris</i>dogmuscleneuromuscular diseaselamininmerosinGeneticsQH426-470ENGenes, Vol 12, Iss 1823, p 1823 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	<i>Canis lupus familiaris</i> dog muscle neuromuscular disease laminin merosin Genetics QH426-470
spellingShingle	<i>Canis lupus familiaris</i> 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 <i>LAMA2</i> Nonsense Variant in an Italian Greyhound with Congenital Muscular Dystrophy
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 <i>LAMA2</i>, 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. <i>LAMA2</i> 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 <i>LAMA2</i> nonsense variant as cause for the CMD phenotype in the investigated dog.
format	article
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	<i>LAMA2</i> Nonsense Variant in an Italian Greyhound with Congenital Muscular Dystrophy
title_short	<i>LAMA2</i> Nonsense Variant in an Italian Greyhound with Congenital Muscular Dystrophy
title_full	<i>LAMA2</i> Nonsense Variant in an Italian Greyhound with Congenital Muscular Dystrophy
title_fullStr	<i>LAMA2</i> Nonsense Variant in an Italian Greyhound with Congenital Muscular Dystrophy
title_full_unstemmed	<i>LAMA2</i> Nonsense Variant in an Italian Greyhound with Congenital Muscular Dystrophy
title_sort	<i>lama2</i> nonsense variant in an italian greyhound with congenital muscular dystrophy
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/312d178b26e94686b4736c82686b1855
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<i>LAMA2</i> Nonsense Variant in an Italian Greyhound with Congenital Muscular Dystrophy

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