3M综合征1例报告并文献复习
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摘要
目的探讨3M综合征的临床特征及致病基因。方法回顾分析1例3M综合征患儿的临床资料,并抽提患儿及父母外周血DNA,通过Agilent Sure Select外显子捕获和Illumina Hi Seq测序平台进行测序分析,同时对发现的突变基因进行Sanger测序法验证。结果女性患儿,6月龄,特殊面容,生长落后。患儿的CUL7基因(NM_014780.4)存在错义变异c.4898C>T,p.T1633M,父母均为杂合突变。确诊为3M综合征。结论患儿为3M综合征主要致病基因CUL7突变。对于临床表型疑似病例应早期进行基因检测以明确诊断。
Objective To investigate the clinical features and gene mutations of 3M syndrome. Method The clinical data of a child with 3M syndrome was retrospectively analyzed. The DNA was extracted from the peripheral blood of the child and parents, and the sequence analyses were performed by Agilent Sure Select exon capture and Illumina Hi Seq sequencing platform. And the mutant gene was validated by Sanger sequencing. Results The six-month-old girl presented special face and growth retardation. The girl had a missense mutation c. 4898 C>T, p.T 1633 M in the CUL 7 gene(NM_014780.4), and both her parents had heterozygous mutations. The girl was diagnosed with 3 M syndrome. Conclusions The CUL 7 mutation is the major causative gene of 3M syndrome in this girl. Early gene testing should be performed to confirm the diagnosis in suspected clinical phenotype.
Objective To investigate the clinical features and gene mutations of 3M syndrome. Method The clinical data of a child with 3M syndrome was retrospectively analyzed. The DNA was extracted from the peripheral blood of the child and parents, and the sequence analyses were performed by Agilent Sure Select exon capture and Illumina Hi Seq sequencing platform. And the mutant gene was validated by Sanger sequencing. Results The six-month-old girl presented special face and growth retardation. The girl had a missense mutation c. 4898 C>T, p.T 1633 M in the CUL 7 gene(NM_014780.4), and both her parents had heterozygous mutations. The girl was diagnosed with 3 M syndrome. Conclusions The CUL 7 mutation is the major causative gene of 3M syndrome in this girl. Early gene testing should be performed to confirm the diagnosis in suspected clinical phenotype.
引文
[1]韩金祥,周小艳.3M综合征//骨骼系统罕见病研究[M].山东:山东大学出版社,2013.
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[3]Güven A1,Cebeci AN.3M syndrome:a report of four cases in two families[J].J Clin Res Pediatr Endocrinol,2011,3(3):154-159.
[4]Holder-Espinasse M,Irving M,Cormier-Daire V.Clinical utility gene card for:3M syndrome[J].Eur J Hum Genet,2011,19(9).doi:10.1038/ejng.2011.32.
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[7]张迪华.陈淳媛.杨作成.Silver-Russel综合征1例[J].中国矫形外科杂志,2002,7(5):406-410.
[8]Gucev ZS,Saranac Lj,Jancevska A,et al.The degree of H19hypomethylation in children with Silver-Russel syndrome(SRS)is not associated with the severity of phenotype and the clinical severity score(CSS)[J].Pril(Makedon Akad Nauk Umet Odd Med Nauki),2013,34(2):79-83.
[9]Kapoor S.Letter to the editor:Dubowitz syndrome:a unique clinical disorder that is often confused with Bloom syndrome[J].J Clin Endocrinol Metab,2015,100(1):L18-L19.
[10]Mc Lachlan K,Pei J,Kully-Martens K,et al.Performanceand questionnaire-based tools for the evaluation of executive function in children and adolescents with fetal alcohol spectru m disorder[J].Int.J Dev Neurosci,2015 Dec;47(Pt A):60.
[11]李异玲,王炳元.胎儿酒精综合征[J].肝脏,2009,14(3):259-260.
[12]Yan J,Yan F,Li Z,et al.The 3M complex maintains microtubule and genome integrity[J].Mol Cell,2014,54(5):791-804.
[13]张鑫、李敏.全基因组外显子测序及其应用[J].遗传,2011,33(8):847-856.
[14]Xu W,Xu J,Shestopaloff K,et al.A genome wide association study on Newfoundland colorectal cancer patients'survival outcomes[J].Biomark Res,2015,3:6.
[15]罗东凤,王少元.全基因组外显子测序及其在遗传病研究中的应用[J].国际遗传学杂志,2012,35(3):173-177.
[16]Clark SL,Aberg KA,Nerella S,et al.Combined whole methylome and genomewide association study implicates CNTN4 in alcohol use[J].Alcohol Clin Exp Res,2015,39(8):1396-1405.
[17]Flex E,Ciolfi A,Caputo V,et al.Loss of function of the E3 ubiquitin-protein ligase UBE3B causes Kaufman oculocerebrofacial syndrome[J].J Med Genet,2013,50(8):493-499.
[18]Deeb A,Afandi O,Attia S,et al.3-M syndrome:a novel CUL7 mutation associated with respiratory distress and a good response to GH therapy[J].Endocrinol Diabetes Metab Case Rep,2015,2015:150012.
[19]Feldmann M,Gilgenkrantz S,Parisot S,et al.3M dwarfism:a study of two further sibs[J].J Med Genet,1989,26(9):583-585.
[20]Harson D,Murray PG,Coulson T,et al.Mutation CUL7,OBSL1 and CCDC8 in 3-M syndrome lead to disordered growth factor signaling[J].J Mol Endocrinol,2012,49(3):267-275.23018678.
[2]Al-Dosari MS,Al-Shammari M,Shaheen R,et al.3M syndrome:an easily recognizable yet underdiagnosed cause of proportionate short stature[J].J Pediatr,2012,161(1):139-145.
[3]Güven A1,Cebeci AN.3M syndrome:a report of four cases in two families[J].J Clin Res Pediatr Endocrinol,2011,3(3):154-159.
[4]Holder-Espinasse M,Irving M,Cormier-Daire V.Clinical utility gene card for:3M syndrome[J].Eur J Hum Genet,2011,19(9).doi:10.1038/ejng.2011.32.
[5]Marshall CR,Farrell SA,Cushing D,et al.Whole-exome analysis of foetal autopsy tssue reveals a frameshift mutation in OBSL1,consistent with a diagnosis of 3-M syndrome[J].BMC Genomics[J].2015,16(Suppl 1),S12.
[6]王卫平.儿科学[M].北京:中国卫生出版社,2015.
[7]张迪华.陈淳媛.杨作成.Silver-Russel综合征1例[J].中国矫形外科杂志,2002,7(5):406-410.
[8]Gucev ZS,Saranac Lj,Jancevska A,et al.The degree of H19hypomethylation in children with Silver-Russel syndrome(SRS)is not associated with the severity of phenotype and the clinical severity score(CSS)[J].Pril(Makedon Akad Nauk Umet Odd Med Nauki),2013,34(2):79-83.
[9]Kapoor S.Letter to the editor:Dubowitz syndrome:a unique clinical disorder that is often confused with Bloom syndrome[J].J Clin Endocrinol Metab,2015,100(1):L18-L19.
[10]Mc Lachlan K,Pei J,Kully-Martens K,et al.Performanceand questionnaire-based tools for the evaluation of executive function in children and adolescents with fetal alcohol spectru m disorder[J].Int.J Dev Neurosci,2015 Dec;47(Pt A):60.
[11]李异玲,王炳元.胎儿酒精综合征[J].肝脏,2009,14(3):259-260.
[12]Yan J,Yan F,Li Z,et al.The 3M complex maintains microtubule and genome integrity[J].Mol Cell,2014,54(5):791-804.
[13]张鑫、李敏.全基因组外显子测序及其应用[J].遗传,2011,33(8):847-856.
[14]Xu W,Xu J,Shestopaloff K,et al.A genome wide association study on Newfoundland colorectal cancer patients'survival outcomes[J].Biomark Res,2015,3:6.
[15]罗东凤,王少元.全基因组外显子测序及其在遗传病研究中的应用[J].国际遗传学杂志,2012,35(3):173-177.
[16]Clark SL,Aberg KA,Nerella S,et al.Combined whole methylome and genomewide association study implicates CNTN4 in alcohol use[J].Alcohol Clin Exp Res,2015,39(8):1396-1405.
[17]Flex E,Ciolfi A,Caputo V,et al.Loss of function of the E3 ubiquitin-protein ligase UBE3B causes Kaufman oculocerebrofacial syndrome[J].J Med Genet,2013,50(8):493-499.
[18]Deeb A,Afandi O,Attia S,et al.3-M syndrome:a novel CUL7 mutation associated with respiratory distress and a good response to GH therapy[J].Endocrinol Diabetes Metab Case Rep,2015,2015:150012.
[19]Feldmann M,Gilgenkrantz S,Parisot S,et al.3M dwarfism:a study of two further sibs[J].J Med Genet,1989,26(9):583-585.
[20]Harson D,Murray PG,Coulson T,et al.Mutation CUL7,OBSL1 and CCDC8 in 3-M syndrome lead to disordered growth factor signaling[J].J Mol Endocrinol,2012,49(3):267-275.23018678.