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- Title
Familial Congenital Methemoglobinemia in Pomeranian Dogs Caused by a Missense Variant in the NADH‐Cytochrome B5 Reductase Gene.
- Authors
Shino, H.; Otsuka‐Yamasaki, Y.; Sato, R.; Yamasaki, M.; Sato, T.; Ooi, K.; Inanami, O.
- Abstract
Background: In veterinary medicine, congenital methemoglobinemia associated with nicotinamide adenine dinucleotide (NADH)‐cytochrome b5 reductase (b5R) deficiency is rare. It has been reported in several breeds of dogs, but little information is available about its etiology. Objectives: To analyze the NADH‐cytochrome b5 reductase gene, <italic>CYB5R3</italic>, in a Pomeranian dog family with methemoglobinemia suspected to be caused by congenital b5R deficiency. Animals: Three Pomeranian dogs from a family with methemoglobinemia were analyzed. Five healthy beagles and 5 nonrelated Pomeranian dogs without methemoglobinemia were used as controls. Methods: Methemoglobin concentration, b5R activity, and reduced glutathione (GSH) concentration were measured, and a turbidity index was used to evaluate Heinz body formation. The <italic>CYB5R3</italic> genes of the affected dog and healthy dogs were analyzed by direct sequencing. Results: Methemoglobin concentrations in erythrocytes of the affected dogs were remarkably higher than those of the control dogs. The b5R activity of the affected dogs was notably lower than that of the control dogs. DNA sequencing indicated that this Pomeranian family carried a <italic>CYB5R3</italic> gene missense variant (ATC→CTC at codon 194) that resulted in the replacement of isoleucine (Ile) by leucine (Leu). Conclusions and Clinical Importance: This dog family had familial congenital methemoglobinemia caused by b5R deficiency, which resulted from a nonsynonymous variant in the <italic>CYB5R3</italic> gene. This variation (c.580A>C) led to an amino acid substitution (p.Ile194Leu), and Ile194 was located in the proximal region of the NADH‐binding motif. Our data suggested that this variant in the canine <italic>CYB5R3</italic> gene would affect function of the b5R in erythrocytes.
- Subjects
METHEMOGLOBINEMIA; NADPH-cytochrome c reductase; POMERANIAN dog; MISSENSE mutation; ETIOLOGY of diseases; FLAVIN adenine dinucleotide; DISEASES; DISEASE risk factors
- Publication
Journal of Veterinary Internal Medicine, 2018, Vol 32, Issue 1, p165
- ISSN
0891-6640
- Publication type
Article
- DOI
10.1111/jvim.15031