目的对我国一个先天性特发性眼球震颤(congenital idiopathic nystagmus,CIN)家系进行基因突变筛查。方法在获取知情同意后,对该家系成员进行病史采集及眼科检查。采集该CIN家系成员及200名正常对照者的外周静脉血各5 m L,并提取基因组...目的对我国一个先天性特发性眼球震颤(congenital idiopathic nystagmus,CIN)家系进行基因突变筛查。方法在获取知情同意后,对该家系成员进行病史采集及眼科检查。采集该CIN家系成员及200名正常对照者的外周静脉血各5 m L,并提取基因组DNA。对FRMD7基因进行引物的设计与合成,使用聚合酶链式反应技术对FRMD7基因的所有编码区序列进行扩增,扩增产物直接测序,寻找突变位点。结果在该CIN家系发现FRMD7基因上c.1003C>T突变,该突变为无义突变(p.R335X)。家系中5例患者均为男性且为该突变的纯合子,3位女性携带者为该突变的杂合子,其余成员和200名正常对照者均未发现此突变。结论该CIN家系致病突变为FRMD7基因上c.1003C>T p.R335X突变。展开更多
Objective:To screen mutations in FERM domain-containing protein 7(FRMD7) gene in two Chinese families with X-linked idiopathic congenital nystagmus(XLICN).Methods:Common ophthalmic data and peripheral blood of two Chi...Objective:To screen mutations in FERM domain-containing protein 7(FRMD7) gene in two Chinese families with X-linked idiopathic congenital nystagmus(XLICN).Methods:Common ophthalmic data and peripheral blood of two Chinese XLICN families(families A and B) were collected after informed consent.Genomic DNA was prepared from the peripheral blood of members of the two families and from 100 normal controls.Mutations in the FRMD7 gene were determined by directly sequencing polymerase chain reaction(PCR) products.Results:We identified a novel mutation c.980_983delATTA compound with c.986C>A mutation in the 11th exon of FRMD7 in family B,and a previously reported splicing mutation c.782G>C(p.R261G) in family A.The mutations were detected in patients and female carriers,while they were absent in other relatives or in the 100 normal controls.Conclusions:Our results expand the spectrum of FRMD7 mutations in association with XLICN,and further confirm that the mutations of FRMD7 are the underlying molecular mechanism for XLICN.展开更多
目的研究一个先天性特发性眼球震颤家系的致病基因。方法选取X染色体上微卫星标记物，通过PCR扩增后，进行基因组扫描。应用GeneMapper软件进行PCR扩增产物片段大小和单倍型分析，Linkage5．1软件进行两点汉连锁值（Log of odds，LOD）...目的研究一个先天性特发性眼球震颤家系的致病基因。方法选取X染色体上微卫星标记物，通过PCR扩增后，进行基因组扫描。应用GeneMapper软件进行PCR扩增产物片段大小和单倍型分析，Linkage5．1软件进行两点汉连锁值（Log of odds，LOD）计算，通过基因序列分析发现致病基因突变。结果经两点法计算，在DXS1047可获最大LOD值为8．55；基因序列分析发现FRMD7基因第9外显子存在G990T的杂合性基因突变。结论FRMD7基因突变是导致该家系出现疾病的主要原因。展开更多
Infant nystagmus sydrome presents as involuntary eye movement disorder and can affect seriously ocular function. We performed a retrospective study of clinical data and FRMD7 genetic test results in 12 cases of infant...Infant nystagmus sydrome presents as involuntary eye movement disorder and can affect seriously ocular function. We performed a retrospective study of clinical data and FRMD7 genetic test results in 12 cases of infantile nystagmus syndrome to correlate waveform, stereopsis, and visual acuity. The patients(age 6.40±2.67 years) had FRMD7 mutations as follows: missense in eight cases, shear in two cases, frameshift in one case, and non-frameshift in one case. Horizontal jerk waveform was observed in six cases, versus horizontal pendulum in five cases and dual jerk in one case. The uncorrected visual acuity(24 eyes) was 0.21±0.12,compared with a corrected visual acuity(24 eyes) of 0.32±0.14. All patients had simultaneous perception, versus fusion function in 10 cases(83.33%) and stereoscopic vision in seven cases(58.33%) using the synoptophore. Eleven cases(91.67%) detected the stereo fly, compared with five cases(41.67%) for stereoscopic circles and seven cases(58.33%) for stereoscopic animals by Titmus test. Stereoscopic vision using the synoptophore did not correlate with the frequency, amplitude, or intensity of nystagmus or with corrected binocular visual acuity. The infantile nystagmus syndrome with FRMD7 mutations in our cases was caused primarily de novo and missense mutations. Visual acuity and binocular visual function were significant impaired, and the waveform was generally horizontal jerk. Also, an infrared videonystagmogram can record the frequency, amplitude, and intensity of nystagmus accurately.展开更多
先天性运动型眼球震颤(Congenital motor nystagmus,CMN)是一种常见的眼科遗传病,在新生儿中发生率较高,具有较高的遗传异质性,其遗传方式包括常染色体显性、常染色体隐性和X连锁等。近年来随着分子生物学技术的发展和在遗传病研究中的...先天性运动型眼球震颤(Congenital motor nystagmus,CMN)是一种常见的眼科遗传病,在新生儿中发生率较高,具有较高的遗传异质性,其遗传方式包括常染色体显性、常染色体隐性和X连锁等。近年来随着分子生物学技术的发展和在遗传病研究中的应用,CMN的遗传学研究取得了较多进展。目前X连锁遗传的CMN致病基因FRMD7已经被定位在Xq26-q27,但对FRMD7基因的功能和致病机制仍需进一步研究。本文对CMN的分子遗传学研究进展进行综述。展开更多
目的·研究1个中国汉族X染色体连锁显性遗传婴儿眼球震颤家系的临床特征。方法·收集上海交通大学医学院附属新华医院眼科就诊的1个X染色体连锁显性遗传婴儿眼球震颤家系,采集所有家系成员外周血进行分子遗传学分析。对家系内5...目的·研究1个中国汉族X染色体连锁显性遗传婴儿眼球震颤家系的临床特征。方法·收集上海交通大学医学院附属新华医院眼科就诊的1个X染色体连锁显性遗传婴儿眼球震颤家系,采集所有家系成员外周血进行分子遗传学分析。对家系内5位患者进行视力、代偿头位扭转角、立体视觉、双眼视功能、视觉电生理检查,及光学相干断层扫描、眼动仪检查和散瞳验光。结果·该家系突变位点为酵母功能域包含蛋白7(FERM domain containing protein 7,FRMD7)基因第9外显子上c.823-829delACCCTAC(p.Thr275fs)移码突变。该家系患者视力多为中度受损,屈光不正为轻度散光性屈光不正,立体视觉下降,双眼可同时视但无法融合,眼球震颤波形为双向冲动型波形,视网膜电图未见明显异常,视觉诱发电位表现多为峰时延迟、振幅降低,光学相干断层扫描未见视网膜黄斑部异常表现,代偿头位表现较为多样。结论·FRMD7蛋白Thr275fs是导致该家系致病的主要原因。该家系患者临床特征表现出一定程度的一致性。展开更多
基金Project supported by the Zhejiang Provincial Science Fund of Health Bureau of China (No. 2012KYA102)the Fundamental Research Funds for the Central Universities (No. 2011FZA7014)+1 种基金the Zhejiang Key Innovation Team Project of China (No. 2009R50039)the Zhejiang Key Laboratory Fund of China (No. 2011E10006)
文摘Objective:To screen mutations in FERM domain-containing protein 7(FRMD7) gene in two Chinese families with X-linked idiopathic congenital nystagmus(XLICN).Methods:Common ophthalmic data and peripheral blood of two Chinese XLICN families(families A and B) were collected after informed consent.Genomic DNA was prepared from the peripheral blood of members of the two families and from 100 normal controls.Mutations in the FRMD7 gene were determined by directly sequencing polymerase chain reaction(PCR) products.Results:We identified a novel mutation c.980_983delATTA compound with c.986C>A mutation in the 11th exon of FRMD7 in family B,and a previously reported splicing mutation c.782G>C(p.R261G) in family A.The mutations were detected in patients and female carriers,while they were absent in other relatives or in the 100 normal controls.Conclusions:Our results expand the spectrum of FRMD7 mutations in association with XLICN,and further confirm that the mutations of FRMD7 are the underlying molecular mechanism for XLICN.
文摘目的研究一个先天性特发性眼球震颤家系的致病基因。方法选取X染色体上微卫星标记物，通过PCR扩增后，进行基因组扫描。应用GeneMapper软件进行PCR扩增产物片段大小和单倍型分析，Linkage5．1软件进行两点汉连锁值（Log of odds，LOD）计算，通过基因序列分析发现致病基因突变。结果经两点法计算，在DXS1047可获最大LOD值为8．55；基因序列分析发现FRMD7基因第9外显子存在G990T的杂合性基因突变。结论FRMD7基因突变是导致该家系出现疾病的主要原因。
基金supported by the capital special features of the Beijing municipal science and technology commission(Z151100004015072)
文摘Infant nystagmus sydrome presents as involuntary eye movement disorder and can affect seriously ocular function. We performed a retrospective study of clinical data and FRMD7 genetic test results in 12 cases of infantile nystagmus syndrome to correlate waveform, stereopsis, and visual acuity. The patients(age 6.40±2.67 years) had FRMD7 mutations as follows: missense in eight cases, shear in two cases, frameshift in one case, and non-frameshift in one case. Horizontal jerk waveform was observed in six cases, versus horizontal pendulum in five cases and dual jerk in one case. The uncorrected visual acuity(24 eyes) was 0.21±0.12,compared with a corrected visual acuity(24 eyes) of 0.32±0.14. All patients had simultaneous perception, versus fusion function in 10 cases(83.33%) and stereoscopic vision in seven cases(58.33%) using the synoptophore. Eleven cases(91.67%) detected the stereo fly, compared with five cases(41.67%) for stereoscopic circles and seven cases(58.33%) for stereoscopic animals by Titmus test. Stereoscopic vision using the synoptophore did not correlate with the frequency, amplitude, or intensity of nystagmus or with corrected binocular visual acuity. The infantile nystagmus syndrome with FRMD7 mutations in our cases was caused primarily de novo and missense mutations. Visual acuity and binocular visual function were significant impaired, and the waveform was generally horizontal jerk. Also, an infrared videonystagmogram can record the frequency, amplitude, and intensity of nystagmus accurately.
文摘先天性运动型眼球震颤(Congenital motor nystagmus,CMN)是一种常见的眼科遗传病,在新生儿中发生率较高,具有较高的遗传异质性,其遗传方式包括常染色体显性、常染色体隐性和X连锁等。近年来随着分子生物学技术的发展和在遗传病研究中的应用,CMN的遗传学研究取得了较多进展。目前X连锁遗传的CMN致病基因FRMD7已经被定位在Xq26-q27,但对FRMD7基因的功能和致病机制仍需进一步研究。本文对CMN的分子遗传学研究进展进行综述。
文摘目的·研究1个中国汉族X染色体连锁显性遗传婴儿眼球震颤家系的临床特征。方法·收集上海交通大学医学院附属新华医院眼科就诊的1个X染色体连锁显性遗传婴儿眼球震颤家系,采集所有家系成员外周血进行分子遗传学分析。对家系内5位患者进行视力、代偿头位扭转角、立体视觉、双眼视功能、视觉电生理检查,及光学相干断层扫描、眼动仪检查和散瞳验光。结果·该家系突变位点为酵母功能域包含蛋白7(FERM domain containing protein 7,FRMD7)基因第9外显子上c.823-829delACCCTAC(p.Thr275fs)移码突变。该家系患者视力多为中度受损,屈光不正为轻度散光性屈光不正,立体视觉下降,双眼可同时视但无法融合,眼球震颤波形为双向冲动型波形,视网膜电图未见明显异常,视觉诱发电位表现多为峰时延迟、振幅降低,光学相干断层扫描未见视网膜黄斑部异常表现,代偿头位表现较为多样。结论·FRMD7蛋白Thr275fs是导致该家系致病的主要原因。该家系患者临床特征表现出一定程度的一致性。
