SCN9A variant in a family of mixed breed dogs with congenital insensitivity to pain.
SCN9A variant in a family of mixed breed dogs with congenital insensitivity to pain.
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DOI：
10.1111/jvim.16610
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发表时间：
2023-01
影响因子：
2.6
通讯作者：
Leeb, Tosso
中科院分区：
文献类型：
--
作者：
Gutierrez-Quintana, Rodrigo;Christen, Matthias;Faller, Kiterie M. E.;Guevar, Julien;Jagannathan, Vidhya;Leeb, Tosso
先天性疼痛不敏感（CIP）和遗传性感觉和自主神经病（HSAN）是一组罕见的遗传性疾病，导致无法感觉疼痛。在犬中发现了三种不同的相关变体：1种在边境牧羊犬中，1种在混种犬中，1种在西班牙猎犬和指示犬中。临床和遗传特征CIP在一个家庭的混合品种的狗。单独提供了来自同一窝的两只混种犬：1只用于评价无痛性骨折，另一只用于评价慢性热皮肤损伤。进行了身体、神经和组织病理学评价。使用1只受影响狗的全基因组测序来鉴定来自不同狗品种的926个对照基因组中不存在的纯合蛋白质改变变体。身体和神经系统检查显示，整个身体没有浅表和深层疼痛感。脑、脊髓和感觉神经节的组织学评价正常。全基因组测序鉴定了SCN 9A中的纯合错义变体，XM_038584713.1：c.2761C>T或XP_038440641.1：（p.Arg921Cys）。两个受影响的狗是纯合子的突变等位基因，这是没有检测到在926只狗的不同品种。我们证实了CIP的诊断在一个家庭的混合品种的狗，并确定了一个可能的致病性变异的SCN9A基因。在这些犬中观察到的临床体征与在具有引起CIP的致病性SCN9A变体的人类中报告的相似。本报告是第一个自发致病性SCN9A变异的家畜。
Congenital insensitivity to pain (CIP) and hereditary sensory and autonomic neuropathies (HSANs) are a rare group of genetic disorders causing inability to feel pain. Three different associated variants have been identified in dogs: 1 in Border Collies, 1 in mixed breed dogs, and 1 in Spaniels and Pointers. To clinically and genetically characterize CIP in a family of mixed breed dogs. Two mixed breed dogs from the same litter were independently presented: 1 for evaluation of painless fractures, and the other for chronic thermal skin injuries. Physical, neurological, and histopathological evaluations were performed. Whole genome sequencing of 1 affected dog was used to identify homozygous protein‐changing variants that were not present in 926 control genomes from diverse dog breeds. Physical and neurological examinations showed the absence of superficial and deep pain perception in the entire body. Histopathological evaluations of the brain, spinal cord and sensory ganglia were normal. Whole genome sequencing identified a homozygous missense variant in SCN9A, XM_038584713.1:c.2761C>T or XP_038440641.1:(p.Arg921Cys). Both affected dogs were homozygous for the mutant allele, which was not detected in 926 dogs of different breeds. We confirmed the diagnosis of CIP in a family of mixed breed dogs and identified a likely pathogenic variant in the SCN9A gene. The clinical signs observed in these dogs mimic those reported in humans with pathogenic SCN9A variants causing CIP. This report is the first of a spontaneous pathogenic SCN9A variant in domestic animals.
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影响因子：
4.3
作者：
Bendl J;Stourac J;Salanda O;Pavelka A;Wieben ED;Zendulka J;Brezovsky J;Damborsky J
通讯作者：
Damborsky J
影响因子：
2.6
作者：
Forman, Oliver P.;Hitti, Rebekkah J.;Mellersh, Cathryn
通讯作者：
Mellersh, Cathryn
影响因子：
1.6
作者：
FRANKLIN, RJM;OLBY, NJ;HOULTON, JEF
通讯作者：
HOULTON, JEF
小鼠和人类缺乏钠通道Na（v）1.7的镇痛的中心机制。
影响因子：
16.2
作者：
MacDonald DI;Sikandar S;Weiss J;Pyrski M;Luiz AP;Millet Q;Emery EC;Mancini F;Iannetti GD;Alles SRA;Arcangeletti M;Zhao J;Cox JJ;Brownstone RM;Zufall F;Wood JN
通讯作者：
Wood JN
影响因子：
2.4
作者：
Jagannathan, V;Droegemueller, C.;Wade, Claire
通讯作者：
Wade, Claire