LAMB3 Missense Variant in Australian Shepherd Dogs with Junctional Epidermolysis Bullosa
In a highly inbred Australian Shepherd litter, three of the five puppies developed widespread ulcers of the skin, footpads, and oral mucosa within the first weeks of life. Histopathological examinations demonstrated clefting of the epidermis from the underlying dermis within or just below the baseme...
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ftdoajarticles:oai:doaj.org/article:dd20ce25a03c48b68d6d01a9ccc3586a 2023-05-15T15:51:03+02:00 LAMB3 Missense Variant in Australian Shepherd Dogs with Junctional Epidermolysis Bullosa Sarah Kiener Aurore Laprais Elizabeth A. Mauldin Vidhya Jagannathan Thierry Olivry Tosso Leeb 2020-09-01T00:00:00Z https://doi.org/10.3390/genes11091055 https://doaj.org/article/dd20ce25a03c48b68d6d01a9ccc3586a EN eng MDPI AG https://www.mdpi.com/2073-4425/11/9/1055 https://doaj.org/toc/2073-4425 doi:10.3390/genes11091055 2073-4425 https://doaj.org/article/dd20ce25a03c48b68d6d01a9ccc3586a Genes, Vol 11, Iss 1055, p 1055 (2020) dog Canis lupus familiaris whole genome sequence wgs dermatology genodermatosis Genetics QH426-470 article 2020 ftdoajarticles https://doi.org/10.3390/genes11091055 2022-12-31T03:56:51Z In a highly inbred Australian Shepherd litter, three of the five puppies developed widespread ulcers of the skin, footpads, and oral mucosa within the first weeks of life. Histopathological examinations demonstrated clefting of the epidermis from the underlying dermis within or just below the basement membrane, which led to a tentative diagnosis of junctional epidermolysis bullosa (JEB) with autosomal recessive inheritance. Endoscopy in one affected dog also demonstrated separation between the epithelium and underlying tissue in the gastrointestinal tract. As a result of the severity of the clinical signs, all three dogs had to be euthanized. We sequenced the genome of one affected puppy and compared the data to 73 control genomes. A search for private variants in 37 known candidate genes for skin fragility phenotypes revealed a single protein-changing variant, LAMB3 :c.1174T>C, or p.Cys392Arg. The variant was predicted to change a conserved cysteine in the laminin β3 subunit of the heterotrimeric laminin-322, which mediates the binding of the epidermal basement membrane to the underlying dermis. Loss-of-function variants in the human LAMB3 gene lead to recessive forms of JEB. We confirmed the expected co-segregation of the genotypes in the Australian Shepherd family. The mutant allele was homozygous in two genotyped cases and heterozygous in three non-affected close relatives. It was not found in 242 other controls from the Australian Shepherd breed, nor in more than 600 other controls. These data suggest that LAMB3 :c.1174T>C represents the causative variant. To the best of our knowledge, this study represents the first report of a LAMB3 -related JEB in domestic animals. Article in Journal/Newspaper Canis lupus Directory of Open Access Journals: DOAJ Articles Genes 11 9 1055 |
institution |
Open Polar |
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Directory of Open Access Journals: DOAJ Articles |
op_collection_id |
ftdoajarticles |
language |
English |
topic |
dog Canis lupus familiaris whole genome sequence wgs dermatology genodermatosis Genetics QH426-470 |
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dog Canis lupus familiaris whole genome sequence wgs dermatology genodermatosis Genetics QH426-470 Sarah Kiener Aurore Laprais Elizabeth A. Mauldin Vidhya Jagannathan Thierry Olivry Tosso Leeb LAMB3 Missense Variant in Australian Shepherd Dogs with Junctional Epidermolysis Bullosa |
topic_facet |
dog Canis lupus familiaris whole genome sequence wgs dermatology genodermatosis Genetics QH426-470 |
description |
In a highly inbred Australian Shepherd litter, three of the five puppies developed widespread ulcers of the skin, footpads, and oral mucosa within the first weeks of life. Histopathological examinations demonstrated clefting of the epidermis from the underlying dermis within or just below the basement membrane, which led to a tentative diagnosis of junctional epidermolysis bullosa (JEB) with autosomal recessive inheritance. Endoscopy in one affected dog also demonstrated separation between the epithelium and underlying tissue in the gastrointestinal tract. As a result of the severity of the clinical signs, all three dogs had to be euthanized. We sequenced the genome of one affected puppy and compared the data to 73 control genomes. A search for private variants in 37 known candidate genes for skin fragility phenotypes revealed a single protein-changing variant, LAMB3 :c.1174T>C, or p.Cys392Arg. The variant was predicted to change a conserved cysteine in the laminin β3 subunit of the heterotrimeric laminin-322, which mediates the binding of the epidermal basement membrane to the underlying dermis. Loss-of-function variants in the human LAMB3 gene lead to recessive forms of JEB. We confirmed the expected co-segregation of the genotypes in the Australian Shepherd family. The mutant allele was homozygous in two genotyped cases and heterozygous in three non-affected close relatives. It was not found in 242 other controls from the Australian Shepherd breed, nor in more than 600 other controls. These data suggest that LAMB3 :c.1174T>C represents the causative variant. To the best of our knowledge, this study represents the first report of a LAMB3 -related JEB in domestic animals. |
format |
Article in Journal/Newspaper |
author |
Sarah Kiener Aurore Laprais Elizabeth A. Mauldin Vidhya Jagannathan Thierry Olivry Tosso Leeb |
author_facet |
Sarah Kiener Aurore Laprais Elizabeth A. Mauldin Vidhya Jagannathan Thierry Olivry Tosso Leeb |
author_sort |
Sarah Kiener |
title |
LAMB3 Missense Variant in Australian Shepherd Dogs with Junctional Epidermolysis Bullosa |
title_short |
LAMB3 Missense Variant in Australian Shepherd Dogs with Junctional Epidermolysis Bullosa |
title_full |
LAMB3 Missense Variant in Australian Shepherd Dogs with Junctional Epidermolysis Bullosa |
title_fullStr |
LAMB3 Missense Variant in Australian Shepherd Dogs with Junctional Epidermolysis Bullosa |
title_full_unstemmed |
LAMB3 Missense Variant in Australian Shepherd Dogs with Junctional Epidermolysis Bullosa |
title_sort |
lamb3 missense variant in australian shepherd dogs with junctional epidermolysis bullosa |
publisher |
MDPI AG |
publishDate |
2020 |
url |
https://doi.org/10.3390/genes11091055 https://doaj.org/article/dd20ce25a03c48b68d6d01a9ccc3586a |
genre |
Canis lupus |
genre_facet |
Canis lupus |
op_source |
Genes, Vol 11, Iss 1055, p 1055 (2020) |
op_relation |
https://www.mdpi.com/2073-4425/11/9/1055 https://doaj.org/toc/2073-4425 doi:10.3390/genes11091055 2073-4425 https://doaj.org/article/dd20ce25a03c48b68d6d01a9ccc3586a |
op_doi |
https://doi.org/10.3390/genes11091055 |
container_title |
Genes |
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11 |
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9 |
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1055 |
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1766386103189766144 |