熊 娟 彭 鏡 段浩林 陳施夢 尹 飛

1 病例資料

表1 7例CDKL5患兒臨床資料

7例患兒起病年齡為22 d至8月齡，中位年齡2月齡。就診年齡為1月齡至8月齡，中位年齡2月齡。病初發(fā)作形式多單一，例3～6表現(xiàn)為部分性發(fā)作、例1～4和7為強直發(fā)作，隨病情進展7例發(fā)作形式、發(fā)作頻次均逐漸增多，均有痙攣發(fā)作表現(xiàn)，例1、3和7肌陣攣發(fā)作也較為常見，例3在4歲7月轉(zhuǎn)化為Lennox-Gastaut綜合征。例7在出現(xiàn)抽搐前即有精神運動發(fā)育落后，表現(xiàn)為3月齡豎頭不穩(wěn)，6月齡不能獨坐，余6例患兒在起病后出現(xiàn)精神運動發(fā)育遲滯。7例均有幼稚面容，例1、2、6和7有異常面容的表現(xiàn)；例4和7有明顯頭圍增長進行減速；例2、5和7有眼球異常運動(斜視、眼球震顫)；部分患兒有吐舌頭、不自主運動異常行為，伴有拍手等手刻板動作；例1和2四肢肌力低、例1～4和7肌張力低。

圖1本文7例患兒CDKL5基因模式圖及突變位點

注 A：CDKL5模式圖及本文7例患兒基因突變位點[例1：c.278dupA (p.E93fs)；例2：c.401G>C (p.G134P)；例3：c.1110del C (p.E370fs)；例4：c.58G>C (p.G20R)；例5：c.464G>A (p.G155D)；例6：c.160-163del (p.K54fs)；例7：3～8號外顯子雜合缺失]；B：CDKL5突變位點分組標準及本文7例患兒分組(a組：aa172前的截短突變致編碼的蛋白無功能/CDKL5整體缺失；b組：激酶區(qū)域內(nèi)的錯義/框內(nèi)突變；c組：aa172～aa781之間的截短突變；d組：aa781(不包含aa781)的截短突變

2 討論

起調(diào)節(jié)表達作用，可以調(diào)節(jié)其激酶活性和核酸定位[17，18]。Fehr研究團隊在既往CDKL5研究成果的基礎(chǔ)上，結(jié)合國際CDKL5綜合征數(shù)據(jù)庫的臨床數(shù)據(jù)，在2015年首次提出將CDKL5突變分為4種類型(見圖1)：①第172個氨基酸前出現(xiàn)截短突變導(dǎo)致催化區(qū)域功能喪失或整個基因缺失；②催化區(qū)域內(nèi)的錯義突變或框內(nèi)突變(如缺失導(dǎo)致一部分激酶區(qū)域功能喪失但其后的蛋白編碼完整)；③第172～781個氨基酸之間的截短突變，包括移碼突變、無義突變等突變類型導(dǎo)致C末端區(qū)域丟失但仍有激酶活性；④第781個氨基酸以后的截短突變，保留了激酶活性及大部分C端區(qū)域。在此分組基礎(chǔ)上，近年來研究表明，D組的CDKL5綜合征患兒智力發(fā)育較其他組別好，在大運動能區(qū)上更可能獨站或獨走，言語能區(qū)上更可能有語言表達發(fā)育[19，20]。本文報告的7個突變位點可應(yīng)用相同分組原則，例1、6和7的突變屬A組，病例2、4和5的突變屬B組，病例3的突變屬C組。結(jié)合Fehr等的研究結(jié)果，這也解釋了本文患兒智力發(fā)育均較差的原因。

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