Detecting the Causal Mutation for Mucopolysaccharidosis IIID in a Nubian Goat Herd in Mexico

Background: Mucopolysaccharidosis type IIID is caused by a deficiency of N-acetylglucosamine-6-sulfatase enzyme, which increases heparan sulfate accumulation in lysosomes and generate cytoplasmic vacuolation in central nervous system and somatic tissues. Goats kids with this disorder exhibit delayed motor development, growth retardation and sudden death. This is a transition mutation of cytosine to thymine at nucleotide 322 of the genetic sequence. The objective of this study was to determine the allelic frequency of the glucosamine N-acetyl-6-sulfatase gene (GNS) that causes mucopolysaccharidosis type IIID (MPS IIID) in a population of Nubian goats in Colima, Mexico. Methods: Genomic DNA was isolated from blood samples of 158 Mexican Nubian goats. The 96 bp fragment of GNS gene including the nonsense mutation was PCR amplified. The PCR amplicon was subjected to RFLP using AluI restriction enzyme to identify polymorphism at nucleotide position 322 (C greater than T). Genotypes were scored. Using Hardy-Weinberg equilibrium (HWE) testing we determined the population to be in genetic equilibrium. Result: Of the entire Nubian goat population genotyped, eight of which were MPS IIID carriers (1 male and 7 females). Observed allelic frequencies were 0.975 for the wild-type allele C and 0.025 for the mutant allele T. MPS IIID was first found in goats at the end of the last century, with considerable higher frequencies, but recent advances in diagnosis and marker-assisted selection against genetic diseases appear to have lowered MPS IIID mutation frequencies in North American Nubian goats. We identified for the first time the variant causing MPS IIID in Nubian goats in Mexico.