Canine junctional epidermolysis bullosa due to a novel mutation in LAMA3 with severe upper respiratory involvement.
Canine junctional epidermolysis bullosa due to a novel mutation in LAMA3 with severe upper respiratory involvement.
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DOI：
10.1111/vde.12972
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发表时间：
2021-08
影响因子：
1.4
通讯作者：
Bizikova P
中科院分区：
文献类型：
--
作者：
Herrmann I;Linder KE;Meurs KM;Friedenberg SG;Cullen J;Olby N;Bizikova P
交界性大疱性表皮松解症（JEB）是一组先天性水疱性皮肤病，其特征是在基底膜区的透明板处发生分裂。
描述一窝患有严重上呼吸道受累的幼犬的一种先天性机械性大疱性疾病的临床和形态学特征，并确定相关的基因变异。
在一窝澳大利亚牧牛犬杂交幼犬中，8只中有5只表现出皮肤脆弱的迹象。3只死产，1只在1个月大时死亡。2只存活的幼犬出现水疱性皮肤病和严重的呼吸窘迫。此外，对1只未患病的同窝幼犬进行了检查，并采集血液进行基因检测。
进行了尸检、组织病理学评估和电子显微镜检查。将1只患病幼犬的全基因组测序（WGS）与55个不同品种的522只狗的数据库进行比较以进行变异分析。对另外1只患病和1只未患病的同窝幼犬进行桑格测序证实了该变异。
临床上，在摩擦部位出现严重的黏膜皮肤溃疡，伴有爪脱落。组织病理学结果显示表皮下裂隙，电子显微镜证实透明板分裂。尸检记录了广泛的咽部和喉部病变，肉芽组织和纤维素性渗出物阻塞气道。中度气管发育不全也起了作用。全基因组测序揭示了层粘连蛋白α3链XP_537297.2p（天冬氨酸2867缬氨酸）的一个新的错义变异，其遗传方式为常染色体隐性遗传。
一种新的变异导致了交界性大疱性表皮松解症的一种全身性且严重的表型，并伴有上呼吸道阻塞的独特临床表现。
Junctional epidermolysis bullosa (JEB) is a group of congenital blistering skin diseases characterized by clefting through the lamina lucida of the basement membrane zone. To characterize the clinical and morphological features of a congenital mechanobullous disease in a litter of puppies with severe upper respiratory involvement, and to identify an associated genetic variant. Five of eight puppies in an Australian cattle dog cross-bred litter showed signs of skin fragility. Three were stillborn and one died at one month of age. The two surviving puppies were presented with blistering skin disease and severe respiratory distress. Additionally, one unaffected sibling was examined, and blood was obtained for genetic testing. Post-mortem examination, histopathological evaluation and electron microscopy were performed. Whole genome sequencing (WGS) of one affected puppy was compared to a database of 522 dogs of 55 different breeds for variant analysis. Sanger sequencing of one additional affected and one unaffected sibling confirmed the variant. Clinically, severe mucocutaneous ulcers occurred in frictional areas with claw sloughing. Histopathological results revealed subepidermal clefts and electron microscopy confirmed the split in the lamina lucida. Post-mortem examination documented extensive pharyngeal and laryngeal lesions with granulation tissue and fibrinous exudate obscuring the airway. Moderate tracheal hypoplasia contributed. The WGS revealed a novel missense variant in the laminin α3-chain XP_537297.2p(Asp2867Val), with an autosomal recessive mode of inheritance. A novel variant caused a generalized and severe phenotype of JEB with an unique clinical presentation of upper-airway obstruction.
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影响因子：
4.8
作者：
Ido, Hiroyuki;Nakamura, Aya;Sekiguchi, Kiyotoshi
通讯作者：
Sekiguchi, Kiyotoshi
影响因子：
2.4
作者：
Jagannathan, V;Droegemueller, C.;Wade, Claire
通讯作者：
Wade, Claire
影响因子：
16.6
作者：
Ishihara J;Ishihara A;Fukunaga K;Sasaki K;White MJV;Briquez PS;Hubbell JA
通讯作者：
Hubbell JA
层粘连蛋白332加工会影响细胞行为。
影响因子：
3.2
作者：
Rousselle P;Beck K
通讯作者：
Beck K
影响因子：
3.5
作者：
Kiener S;Laprais A;Mauldin EA;Jagannathan V;Olivry T;Leeb T
通讯作者：
Leeb T