浅谈神经系统遗传性疾病基因诊断策略及问题
|
摘要
神经系统遗传性疾病临床症状复杂、诊断困难,基因检测是明确诊断的终极手段。近年来分子诊断技术的进步、方法的更新,尤其是二代基因测序技术的广泛应用,使从众多检测方法中选择适宜的基因检测方法成为临床医师的新挑战。本文拟从疾病临床表型出发,结合不同基因突变和基因检测方法,对神经系统单基因遗传病基因诊断策略及问题进行综述。
Neurogenetic diseases are difficult to diagnose due to complicated phenotypes. Genetictesting is always the option for final diagnosis. With the progress and update of molecular diagnostictechniques, especially widely usage of next-generation sequencing(NGS), choosing proper sequencingmethods is a new challenge. This paper aims to review different strategies and problems of geneticdiagnosis for monogenic neurogenetic diseases based on clinical phenotypes, gene mutation characteristicsand gene sequencing methodology.
Neurogenetic diseases are difficult to diagnose due to complicated phenotypes. Genetictesting is always the option for final diagnosis. With the progress and update of molecular diagnostictechniques, especially widely usage of next-generation sequencing(NGS), choosing proper sequencingmethods is a new challenge. This paper aims to review different strategies and problems of geneticdiagnosis for monogenic neurogenetic diseases based on clinical phenotypes, gene mutation characteristicsand gene sequencing methodology.
引文
[1]Xue Y,Ankala A,Wilcox WR,Hegde MR.Solving the molecular diagnostic testing conundrum for Mendelian disorders in the era of next-generation sequencing:single-gene,gene panel,or exome/genome sequencing.Genet Med,2015,17:444-451.
[2]Dong Y,Ni W,Chen WJ,Wan B,Zhao GX,Shi ZQ,Zhang Y,Wang N,Yu L,Xu JF,Wu ZY.Spectrum and Classification of ATP7B Variants in a Large Cohort of Chinese Patients with Wilson's Disease Guides Genetic Diagnosis.Theranostics,2016,6:638-649.
[3]Gess B,Schirmacher A,Boentert M,Young P.Charcot-MarieTooth disease:frequency of genetic subtypes in a German neuromuscular center population.Neuromuscul Disord,2013,23:647-651.
[4]Saporta AS,Sottile SL,Miller LJ,Feely SM,Siskind CE,Shy ME.Charcot-Marie-Tooth disease subtypes and genetic testing strategies.Ann Neurol,2011,69:22-33.
[5]Zhang RX,Tang BS.Classification and molecular diagnostic procedure for Chacort-Marie-Tooth diseas.Zhonghua Yi Xue Yi Chuan Xue Za Zhi,2012,29:553-557.[张如旭,唐北沙.腓骨肌萎缩症的分型与分子诊断流程.中华医学遗传学杂志,2012,29:553-557.]
[6]Birouk N,Gouider R,Guern E,Gugenheim M,Tardieu S,Maisonobe T,Forestier N,Agid Y,Brice A,Bouche P.CharcotMarie-Tooth disease type 1A with 17p11.2 duplication:clinical and electrophysiological phenotype study and factors influencing disease severity in 119 cases.Brain,1997,120:813-823.
[7]Hazan J,Fonknechten N,Mavel D,Paternotte C,Samson D,Artiguenave F,Davoine CS,Cruaud C,Dürr A,Wincker P,Brottier P,Cattolico L,Barbe V,Burgunder JM,Prud'homme JF,Brice A,Fontaine B,Heilig B,Weissenbach J.Spastin,a new AAA protein,is altered in the most frequent form of autosomal dominant spastic paraplegia.Nat Genet,1999,23:296-303.
[8]Sauter SM,Engel W,Neumann LM,Kunze J,Neesen J.Novel mutations in the Atlastin gene(SPG3A)in families with autosomal dominant hereditary spastic paraplegia and evidence for late onset forms of HSP linked to the SPG3A locus.Hum Mutat,2004,23:98.
[9]Hewamadduma C,McDermott C,Kirby J,Grierson A,Panayi M,Dalton A,Rajabally Y,Shaw P.New pedigrees and novel mutation expand the phenotype of REEP1-associated hereditary spastic paraplegia(HSP).Neurogenetics,2009,10:105-110.
[10]Stevanin G,Santorelli FM,Azzedine H,Coutinho P,Chomilier J,Denora PS,Martin E,Ouvrard-Hernandez AM,Tessa A,Bouslam N,Lossos A,Charles P,Loureiro JL,Elleuch N,Confavreux C,Cruz VT,Ruberg M,Leguern E,Grid D,Tazir M,Fontaine B,Filla A,Bertini E,Durr A,Brice A.Mutations in SPG11,encoding spatacsin,are a major cause of spastic paraplegia with thin corpus callosum.Nat Genet,2007,39:366-372.
[11]Rong TY,Chen SD.The clinical features and the strategy of genetic diagnosis in hereditary spastic paraplegia.Zhen Duan Xue Li Lun Yu Shi Jian,2011,10:175-178.[戎天艺,陈生弟.遗传性痉挛性截瘫的临床表现与基因诊断策略.诊断学理论与实践,2011,10:175-178.]
[12]Kumar KR,Blair NF,Vandebona H,Liang C,Ng K,Sharpe DM,Grünewald A,Golnitz U,Saviouk V,Rolfs A,Klein C,Sue CM.Targeted next generation sequencing in SPAST-negative hereditary spastic paraplegia.J Neurol,2013,260:2516-2522.
[13]Balicza P,Grosz Z,Gonzalez MA,Bencsik R,Pentelenyi K,Gal A,Varga E,Klivenyi P,Koller J,Züchner S,Molnar JM.Genetic background of the hereditary spastic paraplegia phenotypes in Hungary-An analysis of 58 probands.J Neurol Sci,2016,364:116-121.
[14]Koutsis G,Lynch DS,Tucci A,Houlden H,Karadima G,Panas M.A novel ABCD1 mutation detected by next generation sequencing in presumed hereditary spastic paraplegia:a 30-year diagnostic delay caused by misleading biochemical findings.J Neurol Sci,2015,355:199-201.
[15]Fuchs T,Saunders—Pullman R,Masuho I,Luciano MS,Raymond D,Factor S,Lang AE,Liang TW,Trosch RM,White S,Ainehsazan E,Herve D,Sharma N,Ehrlich ME,Martemyanov KA,Bressman SB,Ozelius LJ.Mutations in GNAL cause primary torsion dystonia.Nat Genet,2013,45:88-92.
[16]Zech M,Lam DD,Francescatto L,Schormair B,Salminen AV,Jochim A,Wieland T,Lichtner P,Peters A,Gieger C,Lochmüller H,Strom TM,Haslinger B,Katsanis N,Winkelmann J.Recessive mutations in theα3(Ⅵ)collagen gene COL6A3 cause early-onset isolated dystonia.Am J Hum Genet,2015,96:883-893.
[17]Fu XN,Liu AJ,Yang HP,Wei CJ,Ding J,Wang S,Wang JM,Yuan Y,Jiang YW,Xiong H.Application of targeted technology and next generation sequencing in molecular diagnosis of inherit myopathy.Zhonghua Er Ke Za Zhi,2015,53:741-746.[傅晓娜,刘爱杰,杨海坡,魏翠洁,丁娟,王爽,王静敏,袁云,姜玉武,熊晖.靶向捕获二代测序技术在遗传性肌病诊断中的应用.中华儿科杂志,2015,53:741-746.]
[18]Tian X,Liang WC,Feng Y,Wang J,Zhang VW,Chou CH,Huang HD,Lam CW,Hsu YY,Lin TS,Chen WT,Wong LJ,Jong YJ.Expanding genotype/phenotype of neuromuscular diseases by comprehensive target capture/NGS.Neurol Genet,2015,1:E14.
[19]Kuhn M,Glaser D,Joshi PR,Zierz S,Wenninger S,Schoser B,Deschauer M.Utility of a next-generation sequencing-based gene panel investigation in German patients with genetically unclassified limb-girdle muscular dystrophy.J Neurol,2016,263:743-750.
[20]Yang Y,Muzny DM,Reid JG,Bainbridge MN,Willis A,Ward PA,Braxton A,Beuten J,Xia F,Niu Z,Hardison M,Person R,Bekheirnia MR,Leduc MS,Kirby A,Pham P,Scull J,Wang M,Ding Y,Plon SE,Lupski JR,Beaudet AL,Gibbs RA,Eng CM.Clinical whole-exome sequencing for the diagnosis of mendelian disorders.N Engl J Med,2013,369:1502-1511.
[21]Choi M,Scholl UI,Ji W,Liu T,Tikhonova IR,Zumbo P,Nayir A,Bakkaloglu A,Ozen S,Sanjad S,Nelson-Williams C,Farhi A,Mane S,Lifton RP.Genetic diagnosis by whole exome capture and massively parallel DNA sequencing.Proc Natl Acad Sci USA,2009,106:19096-19101.
[22]McCarthy MI,Abecasis GR,Cardon LR,Goldstein DB,Little J,Ioannidis JP,Hirschhorn JN.Genome-wide association studies for complex traits:consensus,uncertainty and challenges.Nat Rev Genet,2008,9:356-369.
[23]Wang JL,Yang X,Xia K,Hu ZM,Weng L,Jin X,Jiang H,Zhang P,Shen L,Guo JF,Li N,Li YR,Lei LF,Zhou J,Du J,Zhou YF,Pan Q,Wang J,Wang J,Li RQ,Tang BS.TGM6identified as a novel causative gene of spinocerebellar ataxias using exome sequencing.Brain,2010,133:3510-3518.
[24]Gilissen C,Hoischen A,Brunner HG,Veltman JA.Disease gene identification strategies for exome sequencing.Eur J Hum Genet,2012,20:490-497.
[25]Richards S,Aziz N,Bale S,Bick D,Das S,Gastier-Foster J,Grody WW,Hegde M,Lyon E,Spector E,Voelkerding K,Rehm HL;ACMG Laboratory Quality Assurance Committee.Standards and guidelines for the interpretation of sequence variants:a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.Genet Med,2015,17:405-424.
[26]Vilarino-Guell C,Wider C,Ross OA,Dachsel JC,Kachergus JM,Lincoln SJ,Soto-Ortolaza AI,Cobb SA,Wilhoite GJ,Bacon JA,Behrouz B,Melrose HL,Hentati E,Puschmann A,Evans DM,Conibear E,Wasserman WW,Aasly JO,Burkhard PR,Djaldetti R,Ghika J,Hentati F,Krygowska-Wajs A,Lynch T,Melamed E,Rajput A,Rajput AH,Solida A,Wu RM,Uitti RJ,Wszolek ZK,Vingerhoets F,Farrer MJ.VPS35 Mutations in Parkinson Disease.Am J Hum Genet,2011,89:162-167.
[27]Vilarino-Güell C,Rajput A,Milnerwood AJ,Shah B,Szu-Tu C,Trinh J,Yu I,Encarnacion M,Munsie LN,Tapia L,Gustavsson EK,Chou P,Tatarnikov I,Evans DM,Pishotta FT,Volta M,Beccano-Kelly D,Thompson C,Lin MK,Sherman HE,Han HJ,Guenther BL,Wasserman WW,Bernard V,Ross CJ,AppelCresswell S,Stoessl AJ,Robinson CA,Dickson DW,Ross OA,Wszolek ZK,Aasly JO,Wu RM,Hentati F,Gibson RA,McPherson PS,Girard M,Rajput M,Rajput AH,Farrer MJ.DNAJC13 mutations in Parkinson disease.Hum Mol Genet,2014,23:1794-1801.
[28]Farlow JL,Robak LA,Hetrick K,Bowling K,Boerwinkle E,Coban-Akdemir ZH,Gambin T,Gibbs RA,Gu S,Jain P,Jankovic J,Jhangiani S,Kaw K,Lai D,Lin H,Ling H,Liu Y,Lupski JR,Muzny D,Porter P,Pugh E,White J,Doheny K,Myers RM,Shulman JM,Foroud T.Whole-exome sequencing in familial Parkinson disease.JAMA Neurol,2016,73:68-75.
[29]Hayden EC.Sequencing set to alter clinical landscape.Nature,2012,482:288.
[30]Bowdin S,Gilbert A,Bedoukian E,Carew C,Adam MP,Belmont J,Bernhardt B,Biesecker L,Bjornsson HT,Blitzer M,D'Alessandro LC,Deardorff MA,Demmer L,Elliott A,Feldman GL,Glass IA,Herman G,Hindorff L,Hisama F,Hudgins L,Innes AM,Jackson L,Jarvik G,Kim R,Korf B,Ledbetter DH,Li M,Liston E,Marshall C,Medne L,Meyn MS,Monfared N,Morton C,Mulvihill JJ,Plon SE,Rehm H,Roberts A,Shuman C,Spinner NB,Stavropoulos DJ,Valverde K,Waggoner DJ,Wilkens A,Cohn RD,Krantz ID.Recommendations for the integration of genomics into clinical practice.Genet Med,2016,18:1075-1084.
[31]Cooperative Group of Application of Chromosomal Microarray Analysis in Prenatal Diagnosis.Expert consensus about application of chromosomal microarray analysis in prenatal diagnosis.Zhonghua Fu Chan Ke Za Zhi,2014,49:570-572.[染色体微阵列分析技术在产前诊断中的应用协作组.染色体微阵列分析技术在产前诊断中的应用专家共识.中华妇产科杂志,2014,49:570-572.]
[32]Sagoo GS,Butterworth AS,Sanderson S,Shaw-Smith C,Higgins JP,Burton H.Array CGH in patients with learning disability(mental retardation)and congenital anomalies:updated systematic review and meta-analysis of 19 studies and 13926subjects.Genet Med,2009,11:139-146.
[33]Yuan HM,Zhu JP,Deng XY,Chen MF,Li XW,Li QL,LüF.Chromosomal microarray analysis of 2000 pediatric cases.Zhonghua Yi Xue Yi Chuan Xue Za Zhi,2016,33:247-251.[袁海明,朱钧萍,邓小燕,陈梦帆,李欣蔚,李秋丽,吕芬.染色体微阵列技术在2000例儿科患者中的应用.中华医学遗传学杂志,2016,33:247-251.]
[34]Roberts JL,Hovanes K,Dasouki M,Manzardo AM,Butler MG.Chromosomal microarray analysis of consecutive individuals with autism spectrum disorders or learning disability presenting for genetic services.Gene,2014,535:70-78.
[35]Schaefer GB,Starr L,Pickering D,Skar G,Dehaai K,Sanger WG.Array comparative genomic hybridization findings in a cohort referred for an autism evaluation.J Child Neurol,2010,25:1498-1503.
[36]Michelson DJ,Shevell MI,Sherr EH,Moeschler JB,Gropman AL,Ashwal S.Evidence report:genetic and metabolic testing on children with global developmental delay:report of the Quality Standards Subcommittee of the American Academy of Neurology and the Practice Committee of the Child Neurology Society.Neurology,2011,77:1629-1635.
[37]Helbig I,Mefford HC,Sharp AJ,Guipponi M,Fichera M,Franke A,Muhle H,de Kovel C,Baker C,von Spiczak S,Kron KL,Steinich I,Kleefuss-Lie AA,Leu C,Gaus V,Schmitz B,Klein KM,Reif PS,Rosenow F,Weber Y,Lerche H,Zimprich F,Urak L,Fuchs K,Feucht M,Genton P,Thomas P,Visscher F,de Haan GJ,M(?)ller RS,Hjalgrim H,Luciano D,Wittig M,Nothnagel M,Elger CE,Nurnberg P,Romano C,Malafosse A,Koeleman BP,Lindhout D,Stephani U,Schreiber S,Eichler EE,Sander T.15ql3.3 microdeletions increase risk of idiopathic generalized epilepsy.Nat Genet,2009,41:160-162.
[38]Dibbens LM,Mullen S,Helbig I,Mefford HC,Bayly MA,Bellows S,Leu C,Trucks H,Obermeier T,Wittig M,Franke A,Caglayan H,Yapici Z;EPICURE Consortium;Sander T,Eichler EE,Scheffer IE,Mulley JC,Berkovic SF.Familial and sporadic15ql3.3 microdeletions in idiopathic generalized epilepsy:precedent for disorders with complex inheritance.Hum Mol Genet,2009,18:3626-3631.
[39]Shoichet SA,Waibel S,Endruhn S,Sperfeld AD,Vorwerk B,Müller I,Erdogan F,Ludolph AC,Ropers HH,Ullmann R.Identification of candidate genes for sporadic amyotrophic lateral sclerosis by array comparative genomic hybridization.Amyotroph Lateral Scler,2009,10:162-169.
[2]Dong Y,Ni W,Chen WJ,Wan B,Zhao GX,Shi ZQ,Zhang Y,Wang N,Yu L,Xu JF,Wu ZY.Spectrum and Classification of ATP7B Variants in a Large Cohort of Chinese Patients with Wilson's Disease Guides Genetic Diagnosis.Theranostics,2016,6:638-649.
[3]Gess B,Schirmacher A,Boentert M,Young P.Charcot-MarieTooth disease:frequency of genetic subtypes in a German neuromuscular center population.Neuromuscul Disord,2013,23:647-651.
[4]Saporta AS,Sottile SL,Miller LJ,Feely SM,Siskind CE,Shy ME.Charcot-Marie-Tooth disease subtypes and genetic testing strategies.Ann Neurol,2011,69:22-33.
[5]Zhang RX,Tang BS.Classification and molecular diagnostic procedure for Chacort-Marie-Tooth diseas.Zhonghua Yi Xue Yi Chuan Xue Za Zhi,2012,29:553-557.[张如旭,唐北沙.腓骨肌萎缩症的分型与分子诊断流程.中华医学遗传学杂志,2012,29:553-557.]
[6]Birouk N,Gouider R,Guern E,Gugenheim M,Tardieu S,Maisonobe T,Forestier N,Agid Y,Brice A,Bouche P.CharcotMarie-Tooth disease type 1A with 17p11.2 duplication:clinical and electrophysiological phenotype study and factors influencing disease severity in 119 cases.Brain,1997,120:813-823.
[7]Hazan J,Fonknechten N,Mavel D,Paternotte C,Samson D,Artiguenave F,Davoine CS,Cruaud C,Dürr A,Wincker P,Brottier P,Cattolico L,Barbe V,Burgunder JM,Prud'homme JF,Brice A,Fontaine B,Heilig B,Weissenbach J.Spastin,a new AAA protein,is altered in the most frequent form of autosomal dominant spastic paraplegia.Nat Genet,1999,23:296-303.
[8]Sauter SM,Engel W,Neumann LM,Kunze J,Neesen J.Novel mutations in the Atlastin gene(SPG3A)in families with autosomal dominant hereditary spastic paraplegia and evidence for late onset forms of HSP linked to the SPG3A locus.Hum Mutat,2004,23:98.
[9]Hewamadduma C,McDermott C,Kirby J,Grierson A,Panayi M,Dalton A,Rajabally Y,Shaw P.New pedigrees and novel mutation expand the phenotype of REEP1-associated hereditary spastic paraplegia(HSP).Neurogenetics,2009,10:105-110.
[10]Stevanin G,Santorelli FM,Azzedine H,Coutinho P,Chomilier J,Denora PS,Martin E,Ouvrard-Hernandez AM,Tessa A,Bouslam N,Lossos A,Charles P,Loureiro JL,Elleuch N,Confavreux C,Cruz VT,Ruberg M,Leguern E,Grid D,Tazir M,Fontaine B,Filla A,Bertini E,Durr A,Brice A.Mutations in SPG11,encoding spatacsin,are a major cause of spastic paraplegia with thin corpus callosum.Nat Genet,2007,39:366-372.
[11]Rong TY,Chen SD.The clinical features and the strategy of genetic diagnosis in hereditary spastic paraplegia.Zhen Duan Xue Li Lun Yu Shi Jian,2011,10:175-178.[戎天艺,陈生弟.遗传性痉挛性截瘫的临床表现与基因诊断策略.诊断学理论与实践,2011,10:175-178.]
[12]Kumar KR,Blair NF,Vandebona H,Liang C,Ng K,Sharpe DM,Grünewald A,Golnitz U,Saviouk V,Rolfs A,Klein C,Sue CM.Targeted next generation sequencing in SPAST-negative hereditary spastic paraplegia.J Neurol,2013,260:2516-2522.
[13]Balicza P,Grosz Z,Gonzalez MA,Bencsik R,Pentelenyi K,Gal A,Varga E,Klivenyi P,Koller J,Züchner S,Molnar JM.Genetic background of the hereditary spastic paraplegia phenotypes in Hungary-An analysis of 58 probands.J Neurol Sci,2016,364:116-121.
[14]Koutsis G,Lynch DS,Tucci A,Houlden H,Karadima G,Panas M.A novel ABCD1 mutation detected by next generation sequencing in presumed hereditary spastic paraplegia:a 30-year diagnostic delay caused by misleading biochemical findings.J Neurol Sci,2015,355:199-201.
[15]Fuchs T,Saunders—Pullman R,Masuho I,Luciano MS,Raymond D,Factor S,Lang AE,Liang TW,Trosch RM,White S,Ainehsazan E,Herve D,Sharma N,Ehrlich ME,Martemyanov KA,Bressman SB,Ozelius LJ.Mutations in GNAL cause primary torsion dystonia.Nat Genet,2013,45:88-92.
[16]Zech M,Lam DD,Francescatto L,Schormair B,Salminen AV,Jochim A,Wieland T,Lichtner P,Peters A,Gieger C,Lochmüller H,Strom TM,Haslinger B,Katsanis N,Winkelmann J.Recessive mutations in theα3(Ⅵ)collagen gene COL6A3 cause early-onset isolated dystonia.Am J Hum Genet,2015,96:883-893.
[17]Fu XN,Liu AJ,Yang HP,Wei CJ,Ding J,Wang S,Wang JM,Yuan Y,Jiang YW,Xiong H.Application of targeted technology and next generation sequencing in molecular diagnosis of inherit myopathy.Zhonghua Er Ke Za Zhi,2015,53:741-746.[傅晓娜,刘爱杰,杨海坡,魏翠洁,丁娟,王爽,王静敏,袁云,姜玉武,熊晖.靶向捕获二代测序技术在遗传性肌病诊断中的应用.中华儿科杂志,2015,53:741-746.]
[18]Tian X,Liang WC,Feng Y,Wang J,Zhang VW,Chou CH,Huang HD,Lam CW,Hsu YY,Lin TS,Chen WT,Wong LJ,Jong YJ.Expanding genotype/phenotype of neuromuscular diseases by comprehensive target capture/NGS.Neurol Genet,2015,1:E14.
[19]Kuhn M,Glaser D,Joshi PR,Zierz S,Wenninger S,Schoser B,Deschauer M.Utility of a next-generation sequencing-based gene panel investigation in German patients with genetically unclassified limb-girdle muscular dystrophy.J Neurol,2016,263:743-750.
[20]Yang Y,Muzny DM,Reid JG,Bainbridge MN,Willis A,Ward PA,Braxton A,Beuten J,Xia F,Niu Z,Hardison M,Person R,Bekheirnia MR,Leduc MS,Kirby A,Pham P,Scull J,Wang M,Ding Y,Plon SE,Lupski JR,Beaudet AL,Gibbs RA,Eng CM.Clinical whole-exome sequencing for the diagnosis of mendelian disorders.N Engl J Med,2013,369:1502-1511.
[21]Choi M,Scholl UI,Ji W,Liu T,Tikhonova IR,Zumbo P,Nayir A,Bakkaloglu A,Ozen S,Sanjad S,Nelson-Williams C,Farhi A,Mane S,Lifton RP.Genetic diagnosis by whole exome capture and massively parallel DNA sequencing.Proc Natl Acad Sci USA,2009,106:19096-19101.
[22]McCarthy MI,Abecasis GR,Cardon LR,Goldstein DB,Little J,Ioannidis JP,Hirschhorn JN.Genome-wide association studies for complex traits:consensus,uncertainty and challenges.Nat Rev Genet,2008,9:356-369.
[23]Wang JL,Yang X,Xia K,Hu ZM,Weng L,Jin X,Jiang H,Zhang P,Shen L,Guo JF,Li N,Li YR,Lei LF,Zhou J,Du J,Zhou YF,Pan Q,Wang J,Wang J,Li RQ,Tang BS.TGM6identified as a novel causative gene of spinocerebellar ataxias using exome sequencing.Brain,2010,133:3510-3518.
[24]Gilissen C,Hoischen A,Brunner HG,Veltman JA.Disease gene identification strategies for exome sequencing.Eur J Hum Genet,2012,20:490-497.
[25]Richards S,Aziz N,Bale S,Bick D,Das S,Gastier-Foster J,Grody WW,Hegde M,Lyon E,Spector E,Voelkerding K,Rehm HL;ACMG Laboratory Quality Assurance Committee.Standards and guidelines for the interpretation of sequence variants:a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.Genet Med,2015,17:405-424.
[26]Vilarino-Guell C,Wider C,Ross OA,Dachsel JC,Kachergus JM,Lincoln SJ,Soto-Ortolaza AI,Cobb SA,Wilhoite GJ,Bacon JA,Behrouz B,Melrose HL,Hentati E,Puschmann A,Evans DM,Conibear E,Wasserman WW,Aasly JO,Burkhard PR,Djaldetti R,Ghika J,Hentati F,Krygowska-Wajs A,Lynch T,Melamed E,Rajput A,Rajput AH,Solida A,Wu RM,Uitti RJ,Wszolek ZK,Vingerhoets F,Farrer MJ.VPS35 Mutations in Parkinson Disease.Am J Hum Genet,2011,89:162-167.
[27]Vilarino-Güell C,Rajput A,Milnerwood AJ,Shah B,Szu-Tu C,Trinh J,Yu I,Encarnacion M,Munsie LN,Tapia L,Gustavsson EK,Chou P,Tatarnikov I,Evans DM,Pishotta FT,Volta M,Beccano-Kelly D,Thompson C,Lin MK,Sherman HE,Han HJ,Guenther BL,Wasserman WW,Bernard V,Ross CJ,AppelCresswell S,Stoessl AJ,Robinson CA,Dickson DW,Ross OA,Wszolek ZK,Aasly JO,Wu RM,Hentati F,Gibson RA,McPherson PS,Girard M,Rajput M,Rajput AH,Farrer MJ.DNAJC13 mutations in Parkinson disease.Hum Mol Genet,2014,23:1794-1801.
[28]Farlow JL,Robak LA,Hetrick K,Bowling K,Boerwinkle E,Coban-Akdemir ZH,Gambin T,Gibbs RA,Gu S,Jain P,Jankovic J,Jhangiani S,Kaw K,Lai D,Lin H,Ling H,Liu Y,Lupski JR,Muzny D,Porter P,Pugh E,White J,Doheny K,Myers RM,Shulman JM,Foroud T.Whole-exome sequencing in familial Parkinson disease.JAMA Neurol,2016,73:68-75.
[29]Hayden EC.Sequencing set to alter clinical landscape.Nature,2012,482:288.
[30]Bowdin S,Gilbert A,Bedoukian E,Carew C,Adam MP,Belmont J,Bernhardt B,Biesecker L,Bjornsson HT,Blitzer M,D'Alessandro LC,Deardorff MA,Demmer L,Elliott A,Feldman GL,Glass IA,Herman G,Hindorff L,Hisama F,Hudgins L,Innes AM,Jackson L,Jarvik G,Kim R,Korf B,Ledbetter DH,Li M,Liston E,Marshall C,Medne L,Meyn MS,Monfared N,Morton C,Mulvihill JJ,Plon SE,Rehm H,Roberts A,Shuman C,Spinner NB,Stavropoulos DJ,Valverde K,Waggoner DJ,Wilkens A,Cohn RD,Krantz ID.Recommendations for the integration of genomics into clinical practice.Genet Med,2016,18:1075-1084.
[31]Cooperative Group of Application of Chromosomal Microarray Analysis in Prenatal Diagnosis.Expert consensus about application of chromosomal microarray analysis in prenatal diagnosis.Zhonghua Fu Chan Ke Za Zhi,2014,49:570-572.[染色体微阵列分析技术在产前诊断中的应用协作组.染色体微阵列分析技术在产前诊断中的应用专家共识.中华妇产科杂志,2014,49:570-572.]
[32]Sagoo GS,Butterworth AS,Sanderson S,Shaw-Smith C,Higgins JP,Burton H.Array CGH in patients with learning disability(mental retardation)and congenital anomalies:updated systematic review and meta-analysis of 19 studies and 13926subjects.Genet Med,2009,11:139-146.
[33]Yuan HM,Zhu JP,Deng XY,Chen MF,Li XW,Li QL,LüF.Chromosomal microarray analysis of 2000 pediatric cases.Zhonghua Yi Xue Yi Chuan Xue Za Zhi,2016,33:247-251.[袁海明,朱钧萍,邓小燕,陈梦帆,李欣蔚,李秋丽,吕芬.染色体微阵列技术在2000例儿科患者中的应用.中华医学遗传学杂志,2016,33:247-251.]
[34]Roberts JL,Hovanes K,Dasouki M,Manzardo AM,Butler MG.Chromosomal microarray analysis of consecutive individuals with autism spectrum disorders or learning disability presenting for genetic services.Gene,2014,535:70-78.
[35]Schaefer GB,Starr L,Pickering D,Skar G,Dehaai K,Sanger WG.Array comparative genomic hybridization findings in a cohort referred for an autism evaluation.J Child Neurol,2010,25:1498-1503.
[36]Michelson DJ,Shevell MI,Sherr EH,Moeschler JB,Gropman AL,Ashwal S.Evidence report:genetic and metabolic testing on children with global developmental delay:report of the Quality Standards Subcommittee of the American Academy of Neurology and the Practice Committee of the Child Neurology Society.Neurology,2011,77:1629-1635.
[37]Helbig I,Mefford HC,Sharp AJ,Guipponi M,Fichera M,Franke A,Muhle H,de Kovel C,Baker C,von Spiczak S,Kron KL,Steinich I,Kleefuss-Lie AA,Leu C,Gaus V,Schmitz B,Klein KM,Reif PS,Rosenow F,Weber Y,Lerche H,Zimprich F,Urak L,Fuchs K,Feucht M,Genton P,Thomas P,Visscher F,de Haan GJ,M(?)ller RS,Hjalgrim H,Luciano D,Wittig M,Nothnagel M,Elger CE,Nurnberg P,Romano C,Malafosse A,Koeleman BP,Lindhout D,Stephani U,Schreiber S,Eichler EE,Sander T.15ql3.3 microdeletions increase risk of idiopathic generalized epilepsy.Nat Genet,2009,41:160-162.
[38]Dibbens LM,Mullen S,Helbig I,Mefford HC,Bayly MA,Bellows S,Leu C,Trucks H,Obermeier T,Wittig M,Franke A,Caglayan H,Yapici Z;EPICURE Consortium;Sander T,Eichler EE,Scheffer IE,Mulley JC,Berkovic SF.Familial and sporadic15ql3.3 microdeletions in idiopathic generalized epilepsy:precedent for disorders with complex inheritance.Hum Mol Genet,2009,18:3626-3631.
[39]Shoichet SA,Waibel S,Endruhn S,Sperfeld AD,Vorwerk B,Müller I,Erdogan F,Ludolph AC,Ropers HH,Ullmann R.Identification of candidate genes for sporadic amyotrophic lateral sclerosis by array comparative genomic hybridization.Amyotroph Lateral Scler,2009,10:162-169.