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A Single Base Insertion in F9 Causing Hemophilia B in a Family of Newfoundland–Parti Standard Poodle Hybrid Dogs

Hemophilia B is an x-linked recessive hereditary coagulopathy that has been reported in various species. We describe a male Newfoundland–Parti Standard Poodle hybrid puppy and its family with hemophilia B from clinical manifestations to the molecular genetic defect. The index case presented for dysp...

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Autores principales: Kuder, Henrike, Sandzhieva-Vuzzo, Liubov, Kehl, Alexandra, Rappaport, Jonathan M., Müller, Elisabeth, Giger, Urs
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8535623/
https://www.ncbi.nlm.nih.gov/pubmed/34680886
http://dx.doi.org/10.3390/genes12101491
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author Kuder, Henrike
Sandzhieva-Vuzzo, Liubov
Kehl, Alexandra
Rappaport, Jonathan M.
Müller, Elisabeth
Giger, Urs
author_facet Kuder, Henrike
Sandzhieva-Vuzzo, Liubov
Kehl, Alexandra
Rappaport, Jonathan M.
Müller, Elisabeth
Giger, Urs
author_sort Kuder, Henrike
collection PubMed
description Hemophilia B is an x-linked recessive hereditary coagulopathy that has been reported in various species. We describe a male Newfoundland–Parti Standard Poodle hybrid puppy and its family with hemophilia B from clinical manifestations to the molecular genetic defect. The index case presented for dyspnea was found to have a mediastinal hematoma, while surgical removal and transfusion support brought some relief, progressive hematoma formations led to humane euthanasia. Sequencing the F9 exons revealed a single nucleotide insertion resulting in a frameshift in the last exon (NM_001003323.2:c.821_822insA), predicted to result in a premature stop codon (NP_001003323.1:p.Asn274LysfsTer23) with a loss of 178 of 459 amino acids. The unexpected high residual plasma factor IX activity (3% to 11% of control) was likely erroneous, but no further studies were performed. Both the purebred Newfoundland dam and her sister were heterozygous for the insertion. Five additional male offspring developed severe hemorrhage and were hemizygous for the F9 variant and/or had a prolonged aPTT. In contrast, other male littermates had normal aPTTs and no evidence of bleeding. While they are related to a common Newfoundland granddam, the prevalence of the pathogenic variant in the Newfoundland breed is currently unknown. These clinical to molecular genetic studies illustrate that precision medicine is achievable in clinical companion animal practice.
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spelling pubmed-85356232021-10-23 A Single Base Insertion in F9 Causing Hemophilia B in a Family of Newfoundland–Parti Standard Poodle Hybrid Dogs Kuder, Henrike Sandzhieva-Vuzzo, Liubov Kehl, Alexandra Rappaport, Jonathan M. Müller, Elisabeth Giger, Urs Genes (Basel) Article Hemophilia B is an x-linked recessive hereditary coagulopathy that has been reported in various species. We describe a male Newfoundland–Parti Standard Poodle hybrid puppy and its family with hemophilia B from clinical manifestations to the molecular genetic defect. The index case presented for dyspnea was found to have a mediastinal hematoma, while surgical removal and transfusion support brought some relief, progressive hematoma formations led to humane euthanasia. Sequencing the F9 exons revealed a single nucleotide insertion resulting in a frameshift in the last exon (NM_001003323.2:c.821_822insA), predicted to result in a premature stop codon (NP_001003323.1:p.Asn274LysfsTer23) with a loss of 178 of 459 amino acids. The unexpected high residual plasma factor IX activity (3% to 11% of control) was likely erroneous, but no further studies were performed. Both the purebred Newfoundland dam and her sister were heterozygous for the insertion. Five additional male offspring developed severe hemorrhage and were hemizygous for the F9 variant and/or had a prolonged aPTT. In contrast, other male littermates had normal aPTTs and no evidence of bleeding. While they are related to a common Newfoundland granddam, the prevalence of the pathogenic variant in the Newfoundland breed is currently unknown. These clinical to molecular genetic studies illustrate that precision medicine is achievable in clinical companion animal practice. MDPI 2021-09-24 /pmc/articles/PMC8535623/ /pubmed/34680886 http://dx.doi.org/10.3390/genes12101491 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Kuder, Henrike
Sandzhieva-Vuzzo, Liubov
Kehl, Alexandra
Rappaport, Jonathan M.
Müller, Elisabeth
Giger, Urs
A Single Base Insertion in F9 Causing Hemophilia B in a Family of Newfoundland–Parti Standard Poodle Hybrid Dogs
title A Single Base Insertion in F9 Causing Hemophilia B in a Family of Newfoundland–Parti Standard Poodle Hybrid Dogs
title_full A Single Base Insertion in F9 Causing Hemophilia B in a Family of Newfoundland–Parti Standard Poodle Hybrid Dogs
title_fullStr A Single Base Insertion in F9 Causing Hemophilia B in a Family of Newfoundland–Parti Standard Poodle Hybrid Dogs
title_full_unstemmed A Single Base Insertion in F9 Causing Hemophilia B in a Family of Newfoundland–Parti Standard Poodle Hybrid Dogs
title_short A Single Base Insertion in F9 Causing Hemophilia B in a Family of Newfoundland–Parti Standard Poodle Hybrid Dogs
title_sort single base insertion in f9 causing hemophilia b in a family of newfoundland–parti standard poodle hybrid dogs
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8535623/
https://www.ncbi.nlm.nih.gov/pubmed/34680886
http://dx.doi.org/10.3390/genes12101491
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