Mucopolysaccharidosis (MPS) VI is a lysosomal storage disease caused by a deficiency of N‐acetylgalactosamine‐4‐sulfatase, also called arylsulfatase B (ARSB, EC 3.1.6.12). Dogs with MPS VI show progressive predominantly oculoskeletal signs homologous to those in human and feline patients. We report herein two pathogenic ARSB gene variants in Miniature Pinscher and Miniature Schnauzer dogs with MPS VI and a genotyping survey in these breeds. All exons and adjacent regions of the ARSB gene were sequenced from three affected Miniature Pinschers and three affected Miniature Schnauzers. Allelic discrimination assays were used for genotyping. A missense variant (NM_001048133.1:c.910G>A) was found in exon 5 of MPS VI‐affected Miniature Pinschers that is predicted to result in a deleterious amino acid substitution of a highly conserved glycine to arginine (NP_001041598.1:p.Gly304Arg). In MPS VI‐affected Miniature Schnauzers, a 56 bp deletion (NM_001048133.1:c.‐24_32del) was found at the junction of exon 1 and its upstream region, predicting no enzyme synthesis. All clinically affected Miniature Pinschers and Miniature Schnauzers were homozygous for the respective variants, and screened healthy dogs in each breed were either heterozygous or homozygous for the wt allele. Whereas the Miniature Pinscher variant seemed to occur commonly (0.133 allele frequency), the Miniature Schnauzer variant was presumed to be rare. In conclusion, two breed‐specific pathogenic ARSB gene variants were identified in Miniature Pinscher and Miniature Schnauzer dogs with MPS VI, allowing for genotyping and informed breeding to prevent the production of affected offspring.

中文翻译：

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导致小型杜宾犬和小型雪纳瑞犬粘多糖贮积症 VI 的 ARSB 基因变异

粘多糖贮积症 (MPS) VI 是一种由N-乙酰半乳糖胺-4-硫酸酯酶（也称为芳基硫酸酯酶 B，ARSB，EC 3.1.6.12）缺乏引起的溶酶体贮积病。患有 MPS VI 的狗表现出与人类和猫科动物患者相似的渐进性主要眼骨骼体征。我们在此报告了具有 MPS VI 的微型杜宾犬和微型雪纳瑞犬的两种致病性ARSB基因变异，以及对这些品种的基因分型调查。ARSB 的所有外显子和相邻区域从三只受影响的小型杜宾犬和三只受影响的小型雪纳瑞犬中对基因进行了测序。等位基因鉴别分析用于基因分型。在受 MPS VI 影响的 Miniature Pinschers 的外显子 5 中发现了一个错义变体 (NM_001048133.1:c.910G>A)，预计该变体会导致高度保守的甘氨酸被有害氨基酸取代为精氨酸 (NP_001041598.1:p .Gly304Arg)。在受 MPS VI 影响的小型雪纳瑞犬中，在外显子 1 及其上游区域的连接处发现了 56 bp 缺失 (NM_001048133.1:c.-24_32del)，预测没有酶合成。所有受临床影响的小型杜宾犬和小型雪纳瑞犬对于各自的变体都是纯合的，并且每个品种中筛选的健康犬的 wt 等位基因要么是杂合的，要么是纯合的。尽管微型杜宾犬变种似乎很常见（等位基因频率为 0.133），但微型雪纳瑞变种被认为是罕见的。总之，两个品种特异性的致病性在具有 MPS VI 的小型短毛猎犬和小型雪纳瑞犬中发现了ARSB基因变异，允许进行基因分型和知情育种，以防止产生受影响的后代。