Genger Seiche C, Mizukami Keijiro, Martin Michael P, Applegate Jeffrey R, Barnes H John, Giger Urs
a Department of Population Health and Pathobiology , College of Veterinary Medicine , Raleigh , NC , USA.
b Section of Medical Genetics, School of Veterinary Medicine , University of Pennsylvania , Philadelphia , PA , USA.
Avian Pathol. 2018 Feb;47(1):100-107. doi: 10.1080/03079457.2017.1380293. Epub 2017 Oct 10.
Clinicopathological diagnosis of mucopolysaccharidosis type IIIB (MPS IIIB; Sanfilippo syndrome B), an inherited autosomal recessive lysosomal storage disease, as a cause of losses in a commercial emu flock and screening breeders using a mutation-specific DNA test are described. Between 2012 and 2015, ∼5-10 juvenile emus from a few weeks to several months of age developed progressive neurological signs and died while others in the flock remained healthy. Necropsy of two affected siblings revealed multiple sites of haemorrhage, cytoplasmic periodic acid-Schiff and Luxol fast blue-positive inclusions in neurons, and aggregates of foamy macrophages in visceral organs. Affected emus were homozygous for the two-base deletion in the α-N-acetylglucosaminidase gene that causes MPS IIIB in emus. Mutation-specific DNA tests for MPS IIIB in emus were developed. Screening blood samples from 78 breeding emus revealed 14 (18%; 9 males, 4 females, and 1 unknown gender) carriers; an overall 0.09 mutant α-N-acetylglucosaminidase allele frequency. A "test and cull male carriers" programme, in which carrier males are culled but carrier females are retained, was proposed to avoid breeding affected emus together, ultimately eliminating the disease from future broods, and preserving the gene pool with as much breeding stock as possible. Molecular genetic diagnostic tests are simple, precise, and permit screening of all breeders for the mutant allele in any flock and can be used to eliminate MPS IIIB-related emu losses through informed breeding.
本文描述了将黏多糖贮积症IIIB型（MPS IIIB；Sanfilippo综合征B型）作为商业鸸鹋种群损失原因的临床病理诊断，MPS IIIB是一种常染色体隐性遗传的溶酶体贮积病，同时还介绍了使用突变特异性DNA检测对种禽进行筛查的情况。在2012年至2015年期间，几只几周至几个月龄的幼年鸸鹋出现进行性神经症状并死亡，而种群中的其他鸸鹋保持健康。对两只患病同胞鸸鹋进行尸检，发现有多处出血、神经元内胞质过碘酸希夫染色和Luxol固蓝染色阳性包涵体，以及内脏器官中泡沫状巨噬细胞聚集。患病鸸鹋在α-N-乙酰氨基葡萄糖苷酶基因中存在导致MPS IIIB的双碱基缺失，呈纯合状态。开发了针对鸸鹋MPS IIIB的突变特异性DNA检测方法。对78只种用鸸鹋的血样进行筛查，发现14只（18%；9只雄性、4只雌性和1只性别不明）携带者；α-N-乙酰氨基葡萄糖苷酶突变等位基因的总体频率为0.09。提出了一项“检测并淘汰雄性携带者”计划，即淘汰携带雄性但保留携带雌性，以避免患病鸸鹋相互交配，最终从未来的雏鸟中消除该病，并尽可能多地保留种禽以保存基因库。分子遗传诊断检测简单、精确，可对任何种群中的所有种禽进行突变等位基因筛查，并可通过明智的育种来消除与MPS IIIB相关的鸸鹋损失。
