色素失禁症一家系NEMO基因突变检测
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摘要
目的:检测中国汉族色素失禁症一家系NEMO基因突变。方法:收集该家系内2例患者及1名正常人外周静脉血和临床资料,提取家系及100名健康对照全基因组DNA,针对NEMO基因外显子区及其侧翼序列设计引物,PCR产物扩增后进行Sanger测序,同时MLPA检测该基因是否存在大片段缺失。结果:该家系2例患者均检测出NEMO基因第5号外显子存在一移码突变c.723_c.724insCAGG,但该家系正常人和100名健康对照个体均未检出此突变。家系内三位被检测者均不存在NEMO基因大片段缺失。结论:该色素失禁症家系内NEMO基因c.723_c.724insCAGG突变可能是其发病的原因。
Objective: To detect the mutation of NEMO gene in a Chinese Han predigree with incontinentia pigmenti(IP). Methods: The data of the predigree, including 2 patients and 1 normal, was collected and DNA was extracted from peripheral blood of the predigree and 100 healthy controls. DNA was amplified and the mutation was detected by sanger sequencing of the exons regions and flanking introns of NEMO gene. The presence of large fragment deletion in this gene was detected by MLPA. Results: A novel frameshift mutation, c.723_c.724-insCAGG in exon 5 was found in NEMO gene in two patients, which was not detected in the normal family member, as well as 100 healthy blood samples. Conclusion: The mutation of c.723_c.724 insCAGG in NEMO gene may be involved in the occurrence of incontinentia pigmenti in this pedigree.
Objective: To detect the mutation of NEMO gene in a Chinese Han predigree with incontinentia pigmenti(IP). Methods: The data of the predigree, including 2 patients and 1 normal, was collected and DNA was extracted from peripheral blood of the predigree and 100 healthy controls. DNA was amplified and the mutation was detected by sanger sequencing of the exons regions and flanking introns of NEMO gene. The presence of large fragment deletion in this gene was detected by MLPA. Results: A novel frameshift mutation, c.723_c.724-insCAGG in exon 5 was found in NEMO gene in two patients, which was not detected in the normal family member, as well as 100 healthy blood samples. Conclusion: The mutation of c.723_c.724 insCAGG in NEMO gene may be involved in the occurrence of incontinentia pigmenti in this pedigree.
引文
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[3] Smahi A,Courtois G,Vabres P,et al.Genomic rearrangement in NEMO impairs NF-κB activation and is a cause of incontinentia pigmenti[J].Nature,2000,405:466-472.
[4] Minic S,Trpinac D,Obradovi'c M.Incontinentia pigmenti diagnostic criteria update[J].Clin Genet,2014,85:536-542.
[5] Narayanan MJ,Rangasamy S,Narayanan V.Incontinentia pigmenti (Bloch -Sulzberger syndrome)[J].Handb Clin Neurol,2015,132:271-280.
[6] Scheuerle AE.Male cases of incontinentia pigmenti:case report and review[J].Am J Med Genet,1998,77:201-218.
[7] Kirchman TT,Levy ML,Lewis RA,et al.Gonadal mosaicism for incontientia -pigmenti in a healthy male[J].J Med Genet,1995,32(11):887-890.
[8] Fusco F,Conte MI,Diociauti A,et al.Unusual father-to-Daughter transmission of incontinentia pigmenti due to mosaicism in IP males[J].Pediatrics,2017,140(3):1-9.
[9] Rafatjoo R,Taghdisi KA.Incontinentia pigmenti;a rare multisystem disorder:case report of a 10-year-old Girl[J].J Dent (Shiraz),2016,17(3):233-237.
[10] Minic S,Trpinac D,Gabriel H,et al.Dental and oral anomalies in incontinentia pigmenti:a systematic review[J].Clin Oral Investig,2013,17:1-8.
[11] Aradhya S,Woffendin H,Jakins T,et al.A recurrent deletion in the ubiquitously expressed NEMO (IKKgamma) gene accounts for the vast majority of incontinentia pigmenti mutations[J].Hum Mol Genet,2001,10:2171-2179.
[12] Maubach G,Naumann M.NEMO links nuclear factor-kB to human diseases[J].Trends in Molecular Medicine,2017,1285:1-18.
[13] Fusco F,Pescatore A,Conte MI,et al.EDA-ID and IP,two faces of the same coin:how the same IKBKG/NEMO mutation affecting the NF-kappaB path -way can cause immunodeficiency and/or inflammation[J].Int Rev Immunol,2015,34:445-459.
[14] Grubisha O,Kaminska M,Duquerroy S,et al.DARPin-assisted crystallography of the CC2-LZ domain of NEMO reveals a coupling between dimerization and ubiquitin binding[J].J Mol Biol,2010,395(1):89-104.
[15] Hayden MS,Ghosh S.NF-kappaB,the first quarter-century:remarkable progress and outstanding questions[J].Gene Dev,2012,26:203-234.
[2] Berlin AL,Paller AS,Chan LS,et al.Incontinentia pigmenti:A review and update on the molecular basis of pathophysiology[J].J Am Acad Dermatol,2002,47:169-187.
[3] Smahi A,Courtois G,Vabres P,et al.Genomic rearrangement in NEMO impairs NF-κB activation and is a cause of incontinentia pigmenti[J].Nature,2000,405:466-472.
[4] Minic S,Trpinac D,Obradovi'c M.Incontinentia pigmenti diagnostic criteria update[J].Clin Genet,2014,85:536-542.
[5] Narayanan MJ,Rangasamy S,Narayanan V.Incontinentia pigmenti (Bloch -Sulzberger syndrome)[J].Handb Clin Neurol,2015,132:271-280.
[6] Scheuerle AE.Male cases of incontinentia pigmenti:case report and review[J].Am J Med Genet,1998,77:201-218.
[7] Kirchman TT,Levy ML,Lewis RA,et al.Gonadal mosaicism for incontientia -pigmenti in a healthy male[J].J Med Genet,1995,32(11):887-890.
[8] Fusco F,Conte MI,Diociauti A,et al.Unusual father-to-Daughter transmission of incontinentia pigmenti due to mosaicism in IP males[J].Pediatrics,2017,140(3):1-9.
[9] Rafatjoo R,Taghdisi KA.Incontinentia pigmenti;a rare multisystem disorder:case report of a 10-year-old Girl[J].J Dent (Shiraz),2016,17(3):233-237.
[10] Minic S,Trpinac D,Gabriel H,et al.Dental and oral anomalies in incontinentia pigmenti:a systematic review[J].Clin Oral Investig,2013,17:1-8.
[11] Aradhya S,Woffendin H,Jakins T,et al.A recurrent deletion in the ubiquitously expressed NEMO (IKKgamma) gene accounts for the vast majority of incontinentia pigmenti mutations[J].Hum Mol Genet,2001,10:2171-2179.
[12] Maubach G,Naumann M.NEMO links nuclear factor-kB to human diseases[J].Trends in Molecular Medicine,2017,1285:1-18.
[13] Fusco F,Pescatore A,Conte MI,et al.EDA-ID and IP,two faces of the same coin:how the same IKBKG/NEMO mutation affecting the NF-kappaB path -way can cause immunodeficiency and/or inflammation[J].Int Rev Immunol,2015,34:445-459.
[14] Grubisha O,Kaminska M,Duquerroy S,et al.DARPin-assisted crystallography of the CC2-LZ domain of NEMO reveals a coupling between dimerization and ubiquitin binding[J].J Mol Biol,2010,395(1):89-104.
[15] Hayden MS,Ghosh S.NF-kappaB,the first quarter-century:remarkable progress and outstanding questions[J].Gene Dev,2012,26:203-234.