The purpose of this study was to report the findings of clinical and genetic evaluation of a 3-month old male Boykin spaniel (the proband) that presented with progressive weakness. The puppy underwent a physical and neurological examination, serum biochemistry and complete blood cell count, electrophysiological testing, muscle biopsy and whole genome sequencing. Clinical evaluation revealed generalized neuromuscular weakness with tetraparesis and difficulty holding the head up and a dropped jaw. There was diffuse spontaneous activity on electromyography, most severe in the cervical musculature. Nerve conduction studies were normal, the findings were interpreted as consistent with a myopathy. Skeletal muscle was grossly abnormal on biopsy and there were necklace fibers and abnormal triad structure localization on histopathology, consistent with myotubular myopathy. Whole genome sequencing revealed a premature stop codon in exon 13 of MTM1 (ChrX: 118,903,496 C > T, c.1467C>T, p.Arg512X). The puppy was humanely euthanized at 5 months of age. The puppy's dam was heterozygous for the variant, and 3 male puppies from a subsequent litter all of which died by 2 weeks of age were hemizygous for the variant. This naturally occurring mutation in Boykin spaniels causes a severe form of X-linked myotubular myopathy, comparable to the human counterpart.

中文翻译：

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MTM1 突变导致博伊金犬 X 连锁肌管肌病

本研究的目的是报告 3 个月大的雄性博伊金猎犬（先证者）的临床和遗传评估结果，该犬表现为进行性虚弱。这只小狗接受了身体和神经系统检查、血清生化和全血细胞计数、电生理测试、肌肉活检和全基因组测序。临床评估显示全身性神经肌肉无力伴四肢瘫痪、抬起头困难和下巴下垂。肌电图有弥漫性自发性活动，最严重的是颈部肌肉组织。神经传导研究正常，结果被解释为与肌病一致。活检显示骨骼肌严重异常，组织病理学显示项链纤维和异常三联结构定位，符合肌管性肌病。全基因组测序显示 MTM1 外显子 13 中存在提前终止密码子（ChrX：118,903,496 C > T，c.1467C>T，p.Arg512X）。这只小狗在 5 个月大时被人道地安乐死。小狗的母犬是该变异体的杂合子，随后一窝中的 3 只雄性幼犬均在 2 周大时死亡，是该变异体的半合子。博伊金猎犬中这种自然发生的突变会导致严重的 X 连锁肌管肌病，与人类对应物相当。来自随后一窝的 3 只雄性幼犬均在 2 周大时死亡，是该变异体的半合子。博伊金猎犬中这种自然发生的突变会导致严重的 X 连锁肌管肌病，与人类对应物相当。来自随后一窝的 3 只雄性幼犬均在 2 周大时死亡，是该变异体的半合子。博伊金猎犬中这种自然发生的突变会导致严重的 X 连锁肌管肌病，与人类对应物相当。