中华医学遗传学杂志
中華醫學遺傳學雜誌
중화의학유전학잡지
CHINESE JOURNAL OF MEDICAL GENETICS
2015年
3期
318-322
,共5页
朱铁山%黄尚志%伍建%汪春丹%杨涛
硃鐵山%黃尚誌%伍建%汪春丹%楊濤
주철산%황상지%오건%왕춘단%양도
神经纤维瘤病Ⅰ型%神经纤维蛋白1基因%目标区域二代测序%基因突变
神經纖維瘤病Ⅰ型%神經纖維蛋白1基因%目標區域二代測序%基因突變
신경섬유류병Ⅰ형%신경섬유단백1기인%목표구역이대측서%기인돌변
Neurofibromatosis type 1%Neurofibromin 1 gene%Targeted next-generation sequencing%Gene mutation
目的 对1例临床拟诊为神经纤维瘤Ⅰ型(neurofibromatosis type 1,NF-1)患者进行致病基因突变研究.方法 通过探针杂交富集患者神经纤维蛋白1 (neurofibromin 1,NF1)基因的全部编码区外显子及其旁侧序列进行高通量测序确定可疑突变,并用Sanger测序法对核心家系成员的相应目标基因区域进行测序验证.结果 在患者NF1基因的第8外显子检出一插入/缺失型突变(indel)c.789790delAGinsT(p.K263Nfs* 18),造成突变点后的三联密码子阅读框发生改变而导致蛋白质翻译的提前终止.其表型正常父母均无此改变.在患者突变点下游第8内含子中还检出两个源自父亲的杂合多态性改变c.888+ 108C＞T(rs2953000)和c.888+ 118G＞T(rs2952999),Sanger测序峰图显示这三处改变位于同一染色体.结论 c.789_790delAGinsT为来自父源的新生突变,确定为患者的致病原因,从而肯定临床诊断.该突变类型补充了NF1基因的突变数据库.比较Sanger测序技术,目标区域二代测序进行NF1基因突变检测,更为快捷、价廉和高效,适用于临床.
目的 對1例臨床擬診為神經纖維瘤Ⅰ型(neurofibromatosis type 1,NF-1)患者進行緻病基因突變研究.方法 通過探針雜交富集患者神經纖維蛋白1 (neurofibromin 1,NF1)基因的全部編碼區外顯子及其徬側序列進行高通量測序確定可疑突變,併用Sanger測序法對覈心傢繫成員的相應目標基因區域進行測序驗證.結果 在患者NF1基因的第8外顯子檢齣一插入/缺失型突變(indel)c.789790delAGinsT(p.K263Nfs* 18),造成突變點後的三聯密碼子閱讀框髮生改變而導緻蛋白質翻譯的提前終止.其錶型正常父母均無此改變.在患者突變點下遊第8內含子中還檢齣兩箇源自父親的雜閤多態性改變c.888+ 108C＞T(rs2953000)和c.888+ 118G＞T(rs2952999),Sanger測序峰圖顯示這三處改變位于同一染色體.結論 c.789_790delAGinsT為來自父源的新生突變,確定為患者的緻病原因,從而肯定臨床診斷.該突變類型補充瞭NF1基因的突變數據庫.比較Sanger測序技術,目標區域二代測序進行NF1基因突變檢測,更為快捷、價廉和高效,適用于臨床.
목적 대1례림상의진위신경섬유류Ⅰ형(neurofibromatosis type 1,NF-1)환자진행치병기인돌변연구.방법 통과탐침잡교부집환자신경섬유단백1 (neurofibromin 1,NF1)기인적전부편마구외현자급기방측서렬진행고통량측서학정가의돌변,병용Sanger측서법대핵심가계성원적상응목표기인구역진행측서험증.결과 재환자NF1기인적제8외현자검출일삽입/결실형돌변(indel)c.789790delAGinsT(p.K263Nfs* 18),조성돌변점후적삼련밀마자열독광발생개변이도치단백질번역적제전종지.기표형정상부모균무차개변.재환자돌변점하유제8내함자중환검출량개원자부친적잡합다태성개변c.888+ 108C＞T(rs2953000)화c.888+ 118G＞T(rs2952999),Sanger측서봉도현시저삼처개변위우동일염색체.결론 c.789_790delAGinsT위래자부원적신생돌변,학정위환자적치병원인,종이긍정림상진단.해돌변류형보충료NF1기인적돌변수거고.비교Sanger측서기술,목표구역이대측서진행NF1기인돌변검측,경위쾌첩、개렴화고효,괄용우림상.
Objective To identify the genetic etiology in a Chinese patient with neurofibromatosis type 1 (NF-1).Methods All coding exons and the flanking sequences of neurofibromin 1 (NF1)gene from the patient were captured,individually barcoded and subjected to HiSeq2000 high-throughput sequencing.Suspected mutation was validated in the nuclear family members with Sanger sequencing.Results A novel indel mutation,c.789_790delAGinsT,was identified in the exon 8 of the NF1 gene in the patient but not in her asymptomatic parents.The mutation was predicted to have caused shifting of the reading frame and a premature downstream stop codon (p.K263Nfs * 18).Two known polymorphisms,c.888 + 108 C＞ T (rs2953000) and c.888 +118 G＞T (rs2952999),was detected in the flanking of the indel mutation in the patient and her father.Sequencing chromatogram for the family indicates that above changes are located on the same chromosome.Conclusion The c.789_790delAGinsT,as a de novo mutation occurring on the paternally derived chromosome,is most likely to be causative for the disease.Compared with Sanger sequencing,targeted next-generation sequencing is more efficient and can dramatically reduce the cost for the genetic testing of NF-1.
