Mucopolysaccharidosis I (Boston Terrier Type)
Affected Genes: IDUA
Inheritance: Autosomal Recessive
Variant(canFam6):
chr3:94001071: 8 bp insertion GGGGGCC
Breed: Boston Terrier
General Information: Mucopolysaccharidosis I (MPS I) in Boston Terriers is caused by a deficiency in the enzyme alpha-L-iduronidase, crucial for the breakdown of glycosaminoglycans (GAGs). This enzyme's deficiency leads to the accumulation of GAGs within various tissues, disrupting normal function. Dogs typically start showing symptoms around the age of 12 months, which can include neurological signs such as ataxia and altered mental status. Physical manifestations may include joint laxity, an abnormal skull shape, cloudiness in the eyes, and hepatomegaly (enlarged liver). Due to the progressive nature of the disease and its impact on quality of life, affected dogs are often euthanized at a young age.
How to Read Your Dog's Test Results for this Genetic Variant:
Two Variants Detected: Dog Likely Affected
One Variant Detected: Dog Unlikely Affected
No Variants Detected: No Effect
Gene / Testing Information: Genetic testing for the IDUA gene is available to determine if Boston Terriers carry the defective gene responsible for Mucopolysaccharidosis I (MPS I). The disease is autosomal recessive, meaning that a dog must inherit two copies of the mutated gene—one from each parent—to exhibit symptoms. Carriers, which possess only one copy of the mutation, typically do not show any symptoms but can produce affected offspring if bred with another carrier. Each breeding of two carriers results in a 25% chance that any given puppy will inherit the disease and a 50% chance that a puppy will be a carrier. It is crucial to perform genetic testing before breeding to prevent the propagation of this debilitating condition. To minimize the risk of producing affected puppies, it is advised not to breed carriers together. Non-carrier dogs are at no increased risk of producing affected offspring.
References:
Dierenfeld AD, McEntee MF, Vogler CA, Vite CH, Chen AH, Passage M, Le S, Shah S, Jens JK, Snella EM, Kline KL, Parkes JD, Ware WA, Moran LE, Fales-Williams AJ, Wengert JA, Whitley RD, Betts DM, Boal AM, Riedesel EA, Gross W, Ellinwood NM, Dickson PI. Replacing the enzyme alpha-L-iduronidase at birth ameliorates symptoms in the brain and periphery of dogs with mucopolysaccharidosis type I. Sci Transl Med. 2010 2(60):60ra89.
Mansour TA, Woolard KD, Vernau KL, Ancona DM, Thomasy SM, Sebbag L, Moore BA, Knipe MF, Seada HA, Cowan TM, Aguilar M, Titus Brown C, Bannasch DL. Whole genome sequencing for mutation discovery in a single case of lysosomal storage disease (MPS type 1) in the dog. Sci Rep. 2020 10(1):6558.
Menon KP, Tieu PT, Neufeld EF. Architecture of the canine IDUA gene and mutation underlying canine mucopolysaccharidosis I. Genomics 1992 14(3):763-768.
Shull RM, Helman RG, Spellacy E, Constantopoulos G, Munger RJ, Neufeld EF. Morphologic and biochemical studies of canine mucopolysaccharidosis I. Am J Pathol. 1984 114(3):487-495.
Shull RM, Munger RJ, Spellacy E, Hall CW, Constantopoulos G, Neufeld EF. Canine alpha-L-iduronidase deficiency. A model of mucopolysaccharidosis I. Am J Pathol. 1982 109(2):244-248
Spellacy E, Shull RM, Constantopoulos G, Neufeld EF. A canine model of human alpha-L-iduronidase deficiency. Proc Natl Acad Sci USA. 1983 80(19):6091-6095.