評估台灣柯基犬及臘腸犬漸進性視網膜退化症及 退化性脊髓神經病變突變盛行率

報告時間：2023-12-15
報告地點：407視聽教室
指導老師： 王建鎧
學生：張晏翎
摘要

      漸進性視網膜退化症 ( progressive retinal atrophy, PRA） 是一種遺傳性視網膜退化疾病，不同犬種中有不同的遺傳模式，錐桿性營養不良（cone–rod dystrophy 1, cord1）的遺傳模式存在臘腸犬中，突變位於RPGRIP1 （retinitis pigmentosa GTPase regulator interacting protein）第2外顯子的44 bp插入；另一種桿錐發育不良3（rod–cone dysplasia 3, RCD3）的遺傳模式存在柯基犬中，突變位於PED6A （phosphodiesterase-6α）第15外顯子的1 bp缺失。犬退化性脊髓神經病變（degenerative myelopathy, DM）是一種漸進性神經退化疾病。超氧化物歧化酶1 （Superoxide Dismutase 1, SOD1） 的兩種單核苷酸置換突變（c.118G > A，c.52A > T），會增加患病風險。因此本研究為探討DM c.118G > A及和PRA相關的兩種突變在台灣柯基犬及臘腸犬中的突變盛行率。從高雄、台中、台南、彰化募集柯基犬及臘腸犬飼主，收集犬隻口腔黏膜進行DNA萃取，利用聚合酶鏈鎖反應(Polymerase chain reaction, PCR)擴增突變片段，以進行基因分型。結合犬隻年齡、性別及診斷資料，分析突變基因的頻率及與疾病的關聯性。檢測46隻臘腸犬，RPGRIP1突變等位基因頻率為0.60，16隻臘腸犬出現PRA-cord1的臨床症狀，患病比例約為34.7%，其中10隻為突變純合子，6隻為雜合子，PRA-cord1與RPGRIP1突變有顯著相關與性別無顯著差異。檢測到的患病犬隻年齡多大於8歲(n=14)，且帶有純合突變的個體在大於8歲的群體中皆有表現出臨床症狀，年齡小於8歲的純合突變的個體(n=4)僅有一隻出現臨床症狀，PRA-cord1與年齡有顯著相關。檢測42隻柯基犬，SOD1突變等為基因頻率為0.65，其中有19隻為突變純合子，17隻為雜合子及6隻野生型。採樣犬隻年齡層較低(小於8歲，n=37)，且並未採樣到患有DM的樣本。綜上所述，RPGRIP1突變會增加臘腸犬患有PRA-cord1的風險，臨床症狀會隨著年齡增長出現。雖未能採樣到患有DM的柯基犬，但根據採樣的柯基犬帶有SOD1突變的比例偏高（45.2%），仍需重視該犬種的疾病預防。未來可增加採樣犬種及篩檢的基因，以建立更完善的犬隻突變基因遺傳檢測及基因頻率及盛行率評估。

關鍵語：漸進性視網膜退化症、退化性脊髓神經病變、RPGRIP1、SOD1、盛行率
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