TY - JOUR
T1 - β-Mannosidosis in German Shepherd Dogs
AU - Jolly, Robert D.
AU - Dittmer, Keren E.
AU - Garrick, Dorian J.
AU - Chernyavtseva, Anastasia
AU - Hemsley, Kim M.
AU - King, Barbara
AU - Fietz, Michael
AU - Shackleton, Nicola M.
AU - Fairley, Robert
AU - Wylie, Kirsten
PY - 2019/9
Y1 - 2019/9
N2 - A neurological disease was investigated in 3 German Shepherd pups from the same litter that failed to grow normally, appeared stiff, were reluctant to move, and were deaf. They developed intermittent seizures and ataxia and had proprioceptive defects. Histopathology showed severe vacuolation of neurons, astrocytes in nervous tissue, renal tubular epithelial cells, and macrophages in nervous tissue, spleen, and liver. Vacuoles appeared empty with no storage material stained by periodic acid–Schiff (PAS) or Sudan black stains, leading to a diagnosis of a lysosomal storage disease and in particular an oligosaccharidosis. Biochemical and genomic studies showed that this was β-mannosidosis, not previously diagnosed in dogs. A c.560T>A transition in exon 4 of the MANBA gene was found, which segregated in these and other family members in a manner consistent with it being the causative mutation of an autosomal recessive disease. This mutation led to substitution of isoleucine to asparagine at position 187 of the 885 amino acid enzyme, a change expected to have functional significance.
AB - A neurological disease was investigated in 3 German Shepherd pups from the same litter that failed to grow normally, appeared stiff, were reluctant to move, and were deaf. They developed intermittent seizures and ataxia and had proprioceptive defects. Histopathology showed severe vacuolation of neurons, astrocytes in nervous tissue, renal tubular epithelial cells, and macrophages in nervous tissue, spleen, and liver. Vacuoles appeared empty with no storage material stained by periodic acid–Schiff (PAS) or Sudan black stains, leading to a diagnosis of a lysosomal storage disease and in particular an oligosaccharidosis. Biochemical and genomic studies showed that this was β-mannosidosis, not previously diagnosed in dogs. A c.560T>A transition in exon 4 of the MANBA gene was found, which segregated in these and other family members in a manner consistent with it being the causative mutation of an autosomal recessive disease. This mutation led to substitution of isoleucine to asparagine at position 187 of the 885 amino acid enzyme, a change expected to have functional significance.
KW - German Shepherd dog
KW - lysosomal storage disease
KW - MANBA
KW - mutation
KW - neurological
KW - whole-genome sequencing
KW - β-mannosidosis
UR - http://www.scopus.com/inward/record.url?scp=85064621584&partnerID=8YFLogxK
U2 - 10.1177/0300985819839239
DO - 10.1177/0300985819839239
M3 - Article
C2 - 30983534
AN - SCOPUS:85064621584
VL - 56
SP - 743
EP - 748
JO - Veterinary Pathology
JF - Veterinary Pathology
SN - 0300-9858
IS - 5
ER -