Two mutations within a feline mucopolysaccharidosis type VI colony cause three different clinical phenotypes

The Journal of Clinical Investigation
A C CrawleyJ J Hopwood

Abstract

Mucopolysaccharidosis type VI (MPS VI) is a lysosomal storage disease caused by a deficiency of N-acetylgalactosamine-4-sulfatase (4S). A feline MPS VI model used to demonstrate efficacy of enzyme replacement therapy is due to the homozygous presence of an L476P mutation in 4-sulfatase. An additional mutation, D520N, inherited independently from L476P and recently identified in the same family of cats, has resulted in three clinical phenotypes. L476P homozygotes exhibit dwarfism and facial dysmorphia due to epiphyseal dysplasia, abnormally low leukocyte 4S/betahexosaminidase ratios, dermatan sulfaturia, lysosomal inclusions in most tissues including chondrocytes, corneal clouding, degenerative joint disease, and abnormal leukocyte inclusions. Similarly, D520N/D520N and L476P/D520N cats have abnormally low leukocyte 4S/betahexosaminidase ratios, mild dermatan sulfaturia, lysosomal inclusions in some chondrocytes, and abnormal leukocyte inclusions. However, both have normal growth and appearance. In addition, L476P/D520N cats have a high incidence of degenerative joint disease. We conclude that L476P/D520N cats have a very mild MPS VI phenotype not previously described in MPS VI humans. The study of L476P/D520N and D520N/ D520N g...Continue Reading

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Citations

Apr 27, 2010·Journal of Feline Medicine and Surgery·Chris TanRichard Malik
Mar 22, 2003·Molecular Genetics and Metabolism·Dyane AuclairAllison C Crawley
Nov 3, 2007·Genome Research·Joan U PontiusStephen J O'Brien
Apr 14, 2010·Orphanet Journal of Rare Diseases·Vassili ValayannopoulosSean Turbeville
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Aug 22, 2021·Molecular Genetics and Metabolism·Eugeni EntchevMireille Tallandier

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