X染色体变异对男性精神发育迟滞致病性的研究进展

doi:10.16288/j.yczz.16-407

遗传 ›› 2017, Vol. 39 ›› Issue (6): 455-468.doi: 10.16288/j.yczz.16-407

X染色体变异对男性精神发育迟滞致病性的研究进展

彭继苹(),刘芳,谢华,陈晓丽()

首都儿科研究所儿童发育营养组学北京市重点实验室,北京100020

收稿日期:2016-11-30 修回日期:2017-01-23 出版日期:2017-06-20 发布日期:2017-03-20
作者简介:彭继苹,硕士研究生,专业方向：分子遗传学。E-mail: 945180106@qq.com|陈晓丽，博士，博士生导师，研究方向：分子遗传学。E-mail: cxlwx@sina.com
基金资助:
国家自然科学基金面上项目(31671310);北京市自然科学基金面上项目(7162029);北京市百千万人才工程创新研发类项目和首都卫生发展科研专项项目(2014-2-1131)

The pathogenicity of genomic/genetic variant of X-chromosomal genes in males with intellectual disability

Peng Jiping(),Liu Fang,Xie Hua,Chen Xiaoli()

Beijing Municipal Key Laboratory of Child Development and Nutriomics, Beijing 100020, China

Received:2016-11-30 Revised:2017-01-23 Online:2017-06-20 Published:2017-03-20
Supported by:
the National Nature Science Foundation of China(31671310);the National Nature Science Foundation of Beijing(7162029);the Innovation Project of Beijing Municipal Human Resources and Social Secutity Bureauand the Capital Health Research and Development of Special(2014-2-1131)

摘要/Abstract

摘要：

精神发育迟滞(旧称智力低下)作为儿科神经科常见的一组疾患,具有高度的遗传和表型异质性,大约25%~50%的精神发育迟滞是由遗传因素引起的,其中X染色体基因/基因组变异占25%~30%,导致X连锁的精神发育迟滞。X连锁的精神发育迟滞患者占所有精神发育迟滞患者的10%~15％以上,约20%~25％的男性精神发育迟滞归因于X连锁的精神发育迟滞。精神发育迟滞男女患病比例为1.3:1,这与男性只有一条X染色体的遗传背景有关。随着新一代基因组检测技术的快速发展和临床应用,尤其是全外显子测序、高深度测序、X染色体深度测序和全基因组芯片杂交,这些大大改善了精神发育迟滞患者的X染色体基因/基因组变异检出。本文综述了致精神发育迟滞的X染色体基因组/基因变异特点、其对男性精神发育迟滞的致病性,以及如何采用新测序技术提高检出率,旨在促进科研人员认识X染色体变异在男性精神发育迟滞的致病性,拓宽精神发育迟滞遗传病因的认识,同时也为遗传咨询和产前诊断提供理论依据。

关键词: 男性精神发育迟滞, X染色体变异, 拷贝数变异, 单核苷酸变异

Abstract:

Intellectual Disability (ID, previously named mental retardation) is a group of common pediatric neurology disorders characterized by extensive genetic and phenotypic heterogeneity. About 25%-50% of ID was caused by genomic/genetic variants, in which genomic/genetic variants of X-chromosome are one of key pathogenic causation (25%-30%), resulting in X-linked ID (XLID). The epidemiological data showed that the male to female ratio is 1.3: 1 in ID patients. The prevalence of XLID in the whole ID population is 10%-15%, and this prevalence reaches 20%-25% in the male ID population. This sex-related differential proportion of ID may be attributed to hemizygosity of X chromosomes in males. A quick detection of genomic/genetic aberrations of X chromosome is feasible and available now due to the overwhelming development of next-generation genomic techniques and their clinical applications; in particular, whole exome sequencing, customer-designed whole genomic chip for the X chromosome, high-density target sequencing and whole X chromosomal sequencing are used widely for clinical diagnosis. In this review, we systematically summarize the pathogenicity and characteristics of X-chromosomal genomic/genetic aberrations in the male patients with ID, and how the new technologies have been used to detect X-chromosomal abnormalities. This review will help researchers understand the pathogenicity of X-chromosomal variations in male ID patients from the view of whole genome, refresh the knowledge about the genomic/genetic etiology of ID, and further provide a theoretical basis for genetic counseling and prenatal diagnosis in the future.

Key words: males with intellectual disability, X-chromosomal variations, copy number variants, single nucleotide variants

彭继苹,刘芳,谢华,陈晓丽. X染色体变异对男性精神发育迟滞致病性的研究进展[J]. 遗传, 2017, 39(6): 455-468.

Peng Jiping,Liu Fang,Xie Hua,Chen Xiaoli. The pathogenicity of genomic/genetic variant of X-chromosomal genes in males with intellectual disability[J]. Hereditas(Beijing), 2017, 39(6): 455-468.

参考文献

[1]	Durkin M. The epidemiology of developmental disabilities in low-income countries. Ment Retard Dev Disabil Res Rev, 2002, 8(3): 206-211.
[2]	Maulik PK, Mascarenhas MN, Mathers CD, Dua T, Saxena S. Prevalence of intellectual disability: a meta-analysis of population-based studies. Res Dev Disabil, 2011, 32(2): 419-436.
[3]	Bauters M, Weuts A, Vandewalle J, Nevelsteen J, Marynen P, Van Esch H, Froyen G. Detection and validation of copy number variation in X-linked mental retardation. Cytogenet Genome Res, 2008, 123(1-4): 44-53.
[4]	Croen LA, Grether JK, Selvin S. The epidemiology of mental retardation of unknown cause. Pediatrics, 2001, 107(6): E86.
[5]	Yeargin-Allxopp M, ‘Murphy CC, Cordrro JF, Decoufle P, Hollowell JG. Reported biomedical causes and associated medical conditions for mental retardation among 10-year-old children, metropolitan Atlanta, 1985 to 1987. Dev Med Child Neurol, 1997, 39(3): 142-149.
[6]	Leonard H, Wen XY. The epidemiology of mental retardation: challenges and opportunities in the new millennium. Ment Retard Dev Disabil Res Rev, 2002, 8(3): 117-134.
[7]	Rauch A, Hoyer J, Guth S, Zweier C, Kraus C, Becker C, Zenker M, Hüffmeier U, Thiel C, Rüschendorf F, Nürnberg P, Reis A, Trautmann U. Diagnostic yield of various genetic approaches in patients with unexplained developmental delay or mental retardation. Am J Med Genet A, 2006, 140A(19): 2063-2074.
[8]	Haldane JBS. A clinical and genetic study of 1280 cases of mental defect. Nature, 1938, 141(3570): 575-576.
[9]	Turner G. X-linked mental retardation. Psychol Med, 1982, 41(3): 55-94.
[10]	Plenge RM, Stevenson RA, Lubs HA, Schwartz CE, Willard HF. Skewed X-chromosome inactivation is a common feature of X-linked mental retardation disorders. Am J Hum Genet, 2002, 71(1): 168-173.
[11]	Carvalho CMB, Bartnik M, Pehlivan D, Fang P, Shen J, Lupski JR. Evidence for disease penetrance relating to CNV size: Pelizaeus-Merzbacher disease and manifesting carriers with a familial 11 Mb duplication at Xq22. Clin Genet, 2012, 81(6): 532-541.
[12]	Turner G. Finding genes on the X chromosome by which homo may have become sapiens. Am J Hum Genet, 1996, 58(6): 1109-1110.
[13]	Kerr B, Turner G, Mulley J, Gedeon A, Partington M. Non-specific X linked mental retardation. J Med Genet, 1991, 28(6): 378-382.
[14]	Mulley JC, Kerr B, Stevenson R, Lubs H. Nomenclature guidelines for X-linked mental retardation. Am J Med Genet, 1992, 43(1-2): 383-391.
[15]	Lubs HA, Stevenson RE, Schwartz CE. Fragile X and X-linked intellectual disability: four decades of discovery. Am J Hum Genet, 2012, 90(4): 579-590.
[16]	Piton A, Redin C, Mandel JL. XLID-causing mutations and associated genes challenged in light of data from large-scale human exome sequencing. Am J Hum Genet, 2013, 93(2): 368-383.
[17]	de Brouwer APM, Yntema HG, Kleefstra T, Lugtenberg D, Oudakker AR, de Vries BBA, van Bokhoven H, Van Esch H, Frints SGM, Froyen G, Fryns JP, Raynaud M, Moizard MP, Ronce N, Bensalem A, Moraine C, Poirier K, Castelnau L, Saillour Y, Bienvenu T, Beldjord C, des Portes V, Chelly J, Turner G, Fullston T, Gecz J, Kuss AW, Tzschach A, Jensen LR, Lenzner S, Kalscheuer VM, Ropers HH, Hamel BCJ. Mutation frequencies of X-linked mental retardation genes in families from the EuroMRX consortium. Hum Mutat, 2007, 28(2): 207-208.
[18]	Tzschach A, Grasshoff U, Beck-Woedl S, Dufke C, Bauer C, Kehrer M, Evers C, Moog U, Oehl-Jaschkowitz B, Di Donato N, Maiwald R, Jung C, Kuechler A, Schulz S, Meinecke P, Spranger S, Kohlhase J, Seidel J, Reif S, Rieger M, Riess A, Sturm M, Bickmann J, Schroeder C, Dufke A, Riess O, Bauer P. Next-generation sequencing in X-linked intellectual disability. Eur J Hum Genet, 2015, 23(11): 1513-1518.
[19]	Nguyen DK, Disteche CM. Dosage compensation of the active X chromosome in mammals. Nat Genet, 2006, 38(1): 47-53.
[20]	Blok LS, Madsen E, Juusola J, Gilissen C, Baralle D, Reijnders MRF, Venselaar H, Helsmoortel C, Cho MT, Hoischen A, Vissers LELM, Koemans T S, Wissink-Lindhout W, Eichler EE, Romano C, Van Esch H, Stumpel C, Vreeburg M, Smeets E, Oberndorff K, van Bon BWM, Shaw M, Gecz J, Haan E, Bienek M, Jensen C, Loeys BL, Van Dijck A, Innes AM, Racher H, Vermeer S, Di Donato N, Rump A, Tatton-Brown K, Parker MJ, Henderson A, Lynch SA, Fryer A, Ross A, Vasudevan P, Kini U, Newbury-Ecob R, Chandler K, Male A, DDD Study, Dijkstra S, Schieving J, Giltay J, van Gassen KLI, Schuurs-Hoeijmakers J, Tan PL, Pediaditakis I, Haas SA, Retterer K, Reed P, Monaghan KG, Haverfield E, Natowicz M, Myers A, Kruer MC, Stein Q, Strauss KA, Brigatti KW, Keating K, Burton BK, Kim KH, Charrow J, Norman J, Foster-Barber A, Kline AD, Kimball A, Zackai E, Harr M, Fox J, McLaughlin J, Lindstrom K, Haude KM, van Roozendaal K, Brunner H, Chung WK, Kooy RF, Pfundt P, Kalscheuer V, Mehta SG, Katsanis N, Kleefstra T. Mutations in DDX3X are a common cause of unexplained intellectual disability with gender-specific effects on wnt signaling. Am J Hum Genet, 2015, 97(2): 343-352.
[21]	Bissar-Tadmouri N, Donahue WL, Al-Gazali L, Nelson SF, Bayrak-Toydemir P, Kantarci S. X chromosome exome sequencing reveals a novel ALG 13 mutation in a nonsyndromic intellectual disability family with multiple affected male siblings. Am J Med Genet A, 2014, 164(1): 164-169.
[22]	Zhang F, Gu WL, Hurles ME, Lupski JR. Copy number variation in human health, disease, and evolution. Annu Rev Genomics Hum Genet, 2009, 10(1): 451-481.
[23]	Buckland PR. Polymorphically duplicated genes: their relevance to phenotypic variation in humans. Ann Med, 2003, 35(5): 308-315.
[24]	Feuk L, Marshall CR, Wintle RF, Scherer SW. Structural variants: changing the landscape of chromosomes and design of disease studies. Hum Mol Genet, 2006, 15(S1): R57-R66.
[25]	Beckmann JS, Estivill X, Antonarakis SE. Copy number variants and genetic traits: closer to the resolution of phenotypic to genotypic variability. Nat Rev Genet, 2007, 8(8): 639-646.
[26]	Cooper GM, Coe BP, Girirajan S, Rosenfeld JA, Vu TH, Baker C, Williams C, Stalker H, Hamid R, Hannig V, Abdel-Hamid H, Bader P, McCracken E, Niyazov D, Leppig K, Thiese H, Hummel M, Alexander N, Gorski J, Kussmann J, Shashi V, Johnson K, Rehder C, Ballif BC, Shaffer LG, Eichler EE. A copy number variation morbidity map of developmental delay. Nat Genet, 2011, 43(9): 838-846.
[27]	Kaminsky EB, Kaul V, Paschall J, Church DM, Bunke B, Kunig D, Moreno-De-Luca D, Moreno-De-Luca A, Mulle JG, Warren ST, Richard G, Compton JG, Fuller AE, Gliem TJ, Huang S, Collinson MN, Beal SJ, Ackley T, Pickering DL, Golden DM, Aston E, Whitby H, Shetty S, Rossi MR, Rudd MK, South ST, Brothman AR, Sanger WG, Iyer RK, Crolla JA, Thorland EC, Aradhya S, Ledbetter DH, Martin CL. An evidence-based approach to establish the functional and clinical significance of copy number variants in intellectual and developmental disabilities. Genet Med, 2011, 13(9): 777-784.
[28]	Slavotinek AM. Novel microdeletion syndromes detected by chromosome microarrays. Hum Genet, 2008, 124(1): 1-17.
[29]	Zahir F, Friedman JM. The impact of array genomic hybridization on mental retardation research: a review of current technologies and their clinical utility. Clin Genet, 2007, 72(4): 271-287.
[30]	El-Hattab AW, Bournat J, Eng PA, Wu JBS, Walker BA, Stankiewicz P, Cheung SW, Brown CW. Microduplication of Xp11.23p11.3 with effects on cognition, behavior, and craniofacial development. Clin Genet, 2011, 79(6): 531-538.
[31]	Froyen G, Bauters M, Boyle J, Van Esch H, Govaerts K, Van Bokhoven H, Ropers HH, Moraine C, Chelly J, Fryns JP. Loss of SLC38A5 and FTSJ1 at Xp11.23 in three brothers with non-syndromic mental retardation due to a microdeletion in an unstable genomic region. Hum Genet, 2007, 121(5): 539-547.
[32]	Van Esch H, Jansen A, Bauters M, Froyen G, Fryns JP. Encephalopathy and bilateral cataract in a boy with an interstitial deletion of Xp22 comprising the CDKL5 and NHS genes. Am J Med Genet A, 2007, 143A(4): 364-369.
[33]	Grams SE, Argiropoulos B, Lines M, Chakraborty P, McGowan-Jordan J, Geraghty MT, Tsang M, Eswara M, Tezcan K, Adams KL, Linck L, Himes P, Kostiner D, Zand DJ, Stalker H, Driscoll DJ, Huang TS, Rosenfeld JA, Li X, Chen E. Genotype-phenotype characterization in 13 individuals with chromosome Xp11.22 duplications. Am J Med Genet A, 2016, 170(4): 967-977.
[34]	Lintas C, Picinelli C, Piras IS, Sacco R, Gabriele S, Verdecchia M, Persico AM. Xp22.33p22.12 duplication in a patient with intellectual disability and dysmorphic facial features. Mol Syndromol, 2016, 6(5): 236-241.
[35]	Basit S, Malibari OI, Al-Balawi AM, Afzal S, Eldardear AEM, Ramzan K. Xq21.31-q21.32 duplication underlies intellectual disability in a large family with five affected males. Am J Med Genet A, 2016, 170(1): 87-93.
[36]	Bonnet C, Grégoire MJ, Brochet K, Raffo E, Leheup B, Jonveaux P. Pure de-novo 5 Mb duplication at Xp11.22- p11.23 in a male: phenotypic and molecular characterization. J Hum Genet, 2006, 51(9): 815-821.
[37]	Marshall CR, Noor A, Vincent JB, Lionel AC, Feuk L, Skaug J, Shago M, Moessner R, Pinto D, Ren Y, Thiruvahindrapduram B, Fiebig A, Schreiber S, Friedman J, Ketelaars CEJ, Vos YJ, Ficicioglu C, Kirkpatrick S, Nicolson R, Sloman L, Summers A, Gibbons CA, Teebi A, Chitayat D, Weksberg R, Thompson A, Vardy C, Crosbie V, Luscombe S, Baatjes R, Zwaigenbaum L, Roberts W, Fernandez B, Szatmari P, Scherer SW. Structural variation of chromosomes in autism spectrum disorder. Am J Hum Genet, 2008, 82(2): 477-488.
[38]	Giorda R, Bonaglia MC, Beri S, Fichera M, Novara F, Magini P, Urquhart J, Sharkey FH, Zucca C, Grasso R, Marelli S, Castiglia L, Di Benedetto D, Musumeci SA, Vitello GA, Failla P, Reitano S, Avola E, Bisulli F, Tinuper P, Mastrangelo M, Fiocchi I, Spaccini L, Torniero C, Fontana E, Lynch SA, Clayton-Smith J, Black G, Jonveaux P, Leheup B, Seri M, Romano C, Dalla Bernardina B, Zuffardi O. Complex segmental duplications mediate a recurrent dup(X)(p11.22-p11.23) associated with mental retardation, speech delay, and EEG anomalies in males and females. Am J Hum Genet, 2009, 85(3): 394-400.
[39]	Whibley AC, Plagnol V, Tarpey PS, Abidi F, Fullston T, Choma MK, Boucher CA, Shepherd L, Willatt L, Parkin G, Smith R, Futreal PA, Shaw M, Boyle J, Licata A, Skinner C, Stevenson RE, Turner G, Field M, Hackett A, Schwartz CE, Gecz J, Stratton MR, Raymond FL. Fine-scale survey of X chromosome copy number variants and indels underlying intellectual disability. Am J Hum Genet, 2010, 87(2): 173-188.
[40]	Zou YX, Liu QJ, Chen BX, Zhang XY, Guo CH, Zhou HB, Li JX, Gao GM, Guo YS, Yan CZ, Wei JJ, Shao CS, Gong YQ. Mutation in CUL4B, which encodes a member of cullin-RING ubiquitin ligase complex, causes X-linked mental retardation. Am J Hum Genet, 2007, 80(3): 561-566.
[41]	Raymond FL, Tarpey PS, Edkins S, Tofts C, O’Meara S, Teague J, Butler A, Stevens C, Barthorpe S, Buck G, Cole J, Dicks E, Gray K, Halliday K, Hills K, Hinton J, Jones D, Menzies A, Perry J, Raine K, Shepherd R, Small A, Varian J, Widaa S, Mallya U, Moon J, Luo Y, Shaw M, Boyle J, Kerr B, Turner G, Quarrell O, Cole T, Easton DF, Wooster R, Bobrow M, Schwartz CE, Gecz J, Stratton MR, Futreal PA. Mutations in ZDHHC9, which encodes a palmitoyltransferase of NRAS and HRAS, cause X-linked mental retardation associated with a Marfanoid habitus. Am J Hum Genet, 2007, 80(5): 982-987.
[42]	Field M, Tarpey PS, Smith R, Edkins S, O'Meara S, Stevens C, Tofts C, Teague J, Butler A, Dicks E, Barthorpe S, Buck G, Cole J, Gray K, Halliday K, Hills K, Jenkinson A, Jones D, Menzies A, Mironenko T, Perry J, Raine K, Richardson D, Shepherd R, Small A, Varian J, West S, Widaa S, Mallya U, Wooster R, Moon J, Luo Y, Hughes H, Shaw M, Friend KL, Corbett M, Turner G, Partington M, Mulley J, Bobrow M, Schwartz C, Stevenson R, Gecz J, Stratton MR, Futreal PA, Raymond FL. Mutations in the BRWD3 gene cause X-linked mental retardation associated with macrocephaly. Am J Hum Genet, 2007, 81(2): 367-374.
[43]	Tarpey PS, Raymond FL, Nguyen LS, Rodriguez J, Hackett A, Vandeleur L, Smith R, Shoubridge C, Edkins S, Stevens C, O'Meara1 S, Tofts C, Barthorpe S, Buck G, Cole J, Halliday K, Hills K, Jones D, Mironenko T, Perry J, Varian J, West S, Widaa S, Teague J, Dicks E, Butler A, Menzies A, Richardson D, Jenkinson A, Shepherd R, Raine K, Moon J, Luo Y, Parnau J, Bhat S S, Gardner A, Corbett M, Brooks D, Thomas P, Parkinson-Lawrence E, Porteous ME, Warner JP, Sanderson T, Pearson P, Simensen RJ, Skinner C, Hoganson G, Superneau D, Wooster R, Bobrow M, Turner G, Stevenson RE, Schwartz CE, Futreal PA, Srivastava AK, Stratton MR, Gécz J. Mutations in UPF3B, a member of the nonsense-mediated mRNA decay complex, cause syndromic and nonsyndromic mental retardation. Nat Genet, 2007, 39(9): 1127-1133.
[44]	Gilfillan GD, Selmer KK, Roxrud I, Smith R, Kyllerman M, Eiklid K, Kroken M, Mattingsdal M, Egeland T, Stenmark H, Sj?holm H, Server A, Samuelsson L, Christianson A, Tarpey P, Whibley A, Stratton MR, Futreal PA, Teague J, Edkins S, Gecz J, Turner G, Raymond FL, Schwartz C, Stevenson RE, Undlien DE, Str?mme P. SLC9A6 mutations cause X-linked mental retardation, microcephaly, epilepsy, and ataxia, a phenotype mimicking Angelman syndrome. Am J Hum Genet, 2008, 82(4): 1003-1010.
[45]	Massin N, Pêcheux C, Eloit C, Bensimon JL, Galey J, Kuttenn F, Hardelin JP, Dodé C, Touraine P. X chromosome-linked Kallmann syndrome: clinical heterogeneity in three siblings carrying an intragenic deletion of the KAL-1 gene. J Clin Endocrinol Metab, 2003, 88(5): 2003-2008.
[46]	S?derlund D, Canto P, Méndez JP. Identification of three novel mutations in the KAL1 gene in patients with Kallmann syndrome. J Clin Endocrinol Metab, 2002, 87(6): 2589-2592.
[47]	Froyen G, Van Esch H, Bauters M, Hollanders K, Frints SGM, Vermeesch JR, Devriendt K, Fryns JP, Marynen P. Detection of genomic copy number changes in patients with idiopathic mental retardation by high-resolution X-array-CGH: important role for increased gene dosage of XLMR genes. Hum Mutat, 2007, 28(10): 1034-1042.
[48]	Najm J, Horn D, Wimplinger I, Golden JA, Chizhikov VV, Sudi J, Christian SL, Ullmann R, Kuechler A, Haas CA, Flubacher A, Charnas LR, Uyanik G, Frank U, Klopocki E, Dobyns WB, Kutsche K. Mutations of CASK cause an X-linked brain malformation phenotype with microcephaly and hypoplasia of the brainstem and cerebellum. Nat Genet, 2008, 40(9): 1065-1067.
[49]	Lugtenberg D, Yntema HG, Banning MJG, Oudakker AR, Firth HV, Willatt L, Raynaud M, Kleefstra T, Fryns JP, Ropers HH, Chelly J, Moraine C, Gécz J, van Reeuwijk J, Nabuurs SB, de Vries BBA, Hamel BCJ, de Brouwer APM, van Bokhoven H.ZNF674: a new krüppel-associated box-containing zinc-finger gene involved in nonsyndromic X-linked mental retardation. Am J Hum Genet, 2006, 78(2): 265-278.
[50]	Zhang LL, Wang T, Wright AF, Suri M, Schwartz CE, Stevenson RE, Valle D. A microdeletion in Xp11.3 accounts for co-segregation of retinitis pigmentosa and mental retardation in a large kindred. Am J Med Genet A, 2006, 140A(4): 349-357.
[51]	Orivoli S, Pavlidis E, Cantalupo G, Pezzella M, Zara F, Garavelli L, Pisani F, Piccolo B. Xp11.22 microduplications including HUWE1: case report and literature review. Neuropediatrics, 2016, 47(1): 51-56.
[52]	Mimault C, Giraud G, Courtois V, Cailloux F, Boire JY, Dastugue B, Boespflug-Tanguy O. Proteolipoprotein gene analysis in 82 patients with sporadic Pelizaeus-Merzbacher disease: duplications, the major cause of the disease, originate more frequently in male germ cells, but point mutations do not. Am J Hum Genet, 1999, 65(2): 360-369.
[53]	Stankiewicz P, Thiele H, Schlicker M, Cseke-Friedrich A, Bartel-Friedrich S, Yatsenko SA, Lupski JR, Hansmann I. Duplication of Xq26.2-q27.1, including SOX3, in a mother and daughter with short stature and dyslalia. Am J Med Genet A, 2005, 138A(1): 11-17.
[54]	del Gaudio D, Fang P, Scaglia F, Ward PA, Craigen WJ, Glaze DG, Neul JL, Patel A, Lee JA, Irons M, Berry SA, Pursley AA, Grebe TA, Freedenberg D, Martin RA, Hsich GE, Khera JR, Friedman NR, Zoghbi HY, Eng CM, Lupski JR, Beaudet AL, Cheung SW, Roa BB. Increased MECP2 gene copy number as the result of genomic duplication in neurodevelopmentally delayed males. Genet Med, 2006, 8(12): 784-792.
[55]	Meins M, Lehmann J, Gerresheim F, Herchenbach J, Hagedorn M, Hameister K, Epplen JT. Submicroscopic duplication in Xq28 causes increased expression of the MECP2 gene in a boy with severe mental retardation and features of Rett syndrome. J Med Genet, 2005, 42(2): e12.
[56]	Friez MJ, Jones JR, Clarkson K, Lubs H, Abuelo D, Bier JAB, Pai S, Simensen R, Williams C, Giampietro PF, Schwartz CE, Stevenson RE. Recurrent infections, hypotonia, and mental retardation caused by duplication of MECP2 and adjacent region in Xq28. Pediatrics, 2006, 118(6): e1687-e1695.
[57]	Madrigal I, Rodríguez-Revenga L, Armengol L, González E, Rodriguez B, Badenas C, Sánchez A, Martínez F, Guitart M, Fernández-Carvajal I, Arranz JA, Tejada MI, Pérez-Jurado LA, Estivill X, Milà M. X-chromosome tiling path array detection of copy number variants in patients with chromosome X-linked mental retardation. BMC Genomics, 2007, 8(1): 443.
[58]	Bauters M, Van Esch H, Friez MJ, Boespflug-Tanguy O, Zenker M, Vianna-Morgante AM, Rosenberg C, Ignatius J, Raynaud M, Hollanders K, Govaerts K, Vandenreijt K, Niel F, Blanc P, Stevenson RE, Fryns JP, Marynen P, Schwartz CE, Froyen G. Nonrecurrent MECP2 duplications mediated by genomic architecture-driven DNA breaks and break-induced replication repair. Genome Res, 2008, 18(6): 847-858.
[59]	Sanlaville D, Schluth-Bolard C, Turleau C. Distal Xq duplication and functional Xq disomy. Orphanet J Rare Dis, 2009, 4(1): 4.
[60]	Kato M, Das S, Petras K, Kitamura K, Morohashi KI, Abuelo DN, Barr M, Bonneau D, Brady AF, Carpenter NJ, Cipero KL, Frisone F, Fukuda T, Guerrini R, Iida E, Itoh M, Lewanda AF, Nanba Y, Oka A, Proud VK, Saugier-Veber P, Schelley SL, Selicorni A, Shaner R, Silengo M, Stewart F, Sugiyama N, Toyama J, Toutain A, Vargas AL, Yanazawa M, Zackai EH, Dobyns WB. Mutations of ARX are associated with striking pleiotropy and consistent genotype-phenotype correlation. Hum Mutat, 2004, 23(2): 147-159.
[61]	Rauch A, Wieczorek D, Graf E, Wieland T, Endele S, Schwarzmayr T, Albrecht B, Bartholdi D, Beygo J, Di Donato N, Dufke A, Cremer K, Hempel M, Horn D, Hoyer J, Joset P, R?pke A, Moog U, Riess A, Thiel CT, Tzschach A, Wiesener A, Wohlleber E, Zweier C, Ekici AB, Zink AM, Rump A, Meisinger C, Grallert H, Sticht H, Schenck A, Engels H, Rappold G, Schr?ck E, Wieacker P, Riess O, Meitinger T, Reis A, Strom TM. Range of genetic mutations associated with severe non-syndromic sporadic intellectual disability: an exome sequencing study. Lancet, 2012, 380(9854): 1674-1682.
[62]	Salomons GS, van Dooren SJM, Verhoeven NM, Cecil KM, Ball WS, Degrauw TJ, Jakobs C. X-linked creatine-transporter gene (SLC6A8) defect: a new creatine-deficiency syndrome. Am J Hum Genet, 2001, 68(6): 1497-1500.
[63]	Bassani S, Cingolani LA, Valnegri P, Folci A, Zapata J, Gianfelice A, Sala C, Goda Y, Passafaro M. The X-linked intellectual disability protein TSPAN7 regulates excitatory synapse development and AMPAR trafficking. Neuron, 2012, 73(6): 1143-1158.
[64]	Laumonnier F, Bonnet-Brilhault F, Gomot M, Blanc R, David A, Moizard MP, Raynaud M, Ronce N, Lemonnier E, Calvas P, Laudier B, Chelly J, Fryns JP, Ropers HH, Hamel BCJ, Andres C, Barthélémy C, Moraine C, Briault S. X-linked mental retardation and autism are associated with a mutation in the NLGN4 gene, a member of the neuroligin family. Am J Hum Genet, 2004, 74(3): 552-557.
[65]	Myers KR, Wang GF, Sheng YH, Conger KK, Casanova JE, Zhu JJ. Arf6-GEF BRAG1 regulates JNK-mediated synaptic removal of GluA1-containing AMPA receptors: a new mechanism for nonsyndromic X-linked mental disorder. J Neurosci, 2012, 32(34): 11716-11726.
[66]	Mendoza RB, Labastilla EM, Endriga MA, Deocaris CC, Deocaris CC. Systems analysis of X-chromosomal miRNAs and their target genes using informatics tools. J Trends Chem, 2010, 1(1): 18-23.
[67]	Wu Y, Arai AC, Rumbaugh G, Srivastava AK, Turner G, Hayashi T, Suzuki E, Jiang YW, Zhang LL, Rodriguez J, Boyle J, Tarpey P, Raymond FL, Nevelsteen J, Froyen G, Stratton M, Futreal A, Gecz J, Stevenson R, Schwartz CE, Valle D, Huganir RL, Wang T. Mutations in ionotropic ampa receptor 3 alter channel properties and are associated with moderate cognitive impairment in humans. Proc Natl Acad Sci USA, 2007, 104(46): 18163-18168.
[68]	Yi YH, Sun XS, Qin JM, Zhao QH, Liao WP, Long YS. Experimental identification of microRNA targets on the 3' untranslated region of human FMR1 gene. J Neurosci Methods, 2010, 190(1): 34-38.
[69]	Cheever A, Blackwell E, Ceman S. Fragile X protein family member FXR1P is regulated by microRNAs. RNA, 2010, 16(8): 1530-1539.
[70]	Xu XL, Zong RT, Li ZD, Biswas MH, Fang Z, Nelson DL, Gao FB. FXR1P but not FMRP regulates the levels of mammalian brain-specific microRNA-9 and microRNA-124. J Neurosci, 2011, 31(39): 13705-13709.
[71]	Gécz J, Shoubridge C, Corbett M. The genetic landscape of intellectual disability arising from chromosome X. Trends Genet, 2009, 25(7): 308-316.
[72]	Baker K, Raymond FL, Bass N. Genetic investigation for adults with intellectual disability: opportunities and challenges. Curr Opin Neurol, 2012, 25(2): 150-158.
[73]	Zarate YA, Dwivedi A, Bartel FO, Bellomo MA, Cathey SS, Champaigne NL, Clarkson LK, Dupont BR, Everman DB, Geer JS, Gordon BC, Lichty AW, Lyons MJ, Rogers RC, Saul RA, Schroer RJ, Skinner SA, Stevenson RE. Clinical utility of the X-chromosome array. Am J Med Genet A, 2013, 161A(1): 120-130.
[74]	Shimojima K, Inoue T, Hoshino A, Kakiuchi S, Watanabe Y, Sasaki M, Nishimura A, Takeshita-Yanagisawa A, Tajima G, Ozawa H, Kubota M, Tohyama J, Sasaki M, Oka A, Saito K, Osawa M, Yamamoto T. Comprehensive genetic analyses of PLP1 in patients with Pelizaeus-Merzbacher disease applied by array-CGH and fiber-FISH analyses identified new mutations and variable sizes of duplications. Brain Dev, 2010, 32(3): 171-179.
[75]	Froyen G, Bauters M, Boyle J,, Van Esch H, Govaerts K, Van BH, Ropers HH, Moraine C, Chelly J, Fryns JP, Marynen P, Gecz J, Turner G. Loss of SLC38A5 and FTSJ1 at Xp11.23 in three brothers with non-syndromic mental retardation due to a microdeletion in an unstable genomic region. Hum Genet, 2007, 121(5): 539-547.
[76]	Veltman JA, Yntema HG, Lugtenberg D, Arts H, Briault S, Huys EHLPG, Osoegawa K, de Jong P, Brunner HG, van Kessel AG, van Bokhoven H, Schoenmakers EFPM. High resolution profiling of X chromosomal aberrations by array comparative genomic hybridisation. J Med Genet, 2004, 41(6): 425-432.
[77]	Bauters M, Van Esch H, Marynen P, Froyen G. X chromosome array-CGH for the identification of novel X-linked mental retardation genes. Eur J Med Genet, 2005, 48(3): 263-275.
[78]	Hayashi S, Honda S, Minaguchi M, Makita Y, Okamoto N, Kosaki R, Okuyama T, Imoto I, Mizutani S, Inazawa J. Construction of a high-density and high-resolution human chromosome X array for comparative genomic hybridization analysis. J Hum Genet, 2007, 52(5): 397-405.
[79]	Lugtenberg D, De Brouwer APM, Kleefstra T, Oudakker AR, Frints SGM, Schrander-Stumpel CTRM, Fryns JP, Jensen LR, Chelly J, Moraine C, Turner G, Veltman JA, Hamel BCJ, De Vries BBA, Van Bokhoven H, Yntema HG. Chromosomal copy number changes in patients with non-syndromic X linked mental retardation detected by array CGH. J Med Genet, 2006, 43(4): 362-370.
[80]	Mignon-Ravix C, Cacciagli P, Choucair N, Popovici C, Missirian C, Milh M, Mégarbané A, Busa T, Julia S, Girard N, Badens C, Sigaudy S, Philip N, Villard L. Intragenic rearrangements in X-linked intellectual deficiency: results of a-CGH in a series of 54 patients and identification of TRPC5 and KLHL15 as potential XLID genes. Am J Med Genet A, 2014, 164(8): 1991-1997.
[81]	Tarpey PS, Smith R, Pleasance E, Whibley A, Edkins S, Hardy C, O'Meara S, Latimer C, Dicks E, Menzies A, Stephens P, Blow M, Greenman C, Xue YL, Tyler-Smith C, Thompson D, Gray K, Andrews J, Barthorpe S, Buck G, Cole J, Dunmore R, Jones D, Maddison M, Mironenko T, Turner R, Turrell K, Varian J, West S, Widaa S, Wray P, Teague J, Butler A, Jenkinson A, Jia MM, Richardson D, Shepherd R, Wooster R, Tejada MI, Martinez F, Carvill G, Goliath R, de Brouwer APM, van Bokhoven H, Van Esch H, Chelly J, Raynaud M, Ropers HH, Abidi FE, Srivastava AK, Cox J, Luo Y, Mallya U, Moon J, Parnau J, Mohammed S, Tolmie JL, Shoubridge C, Corbett M, Gardner A, Haan E, Rujirabanjerd S, Shaw M, Vandeleur L, Fullston T, Easton DF, Boyle J, Partington M, Hackett A, Field M, Skinner C, Stevenson RE, Bobrow M, Turner G, Schwartz CE, Gecz J, Raymond FL, Futreal PA, Stratton MR. A systematic, large-scale resequencing screen of X-chromosome coding exons in mental retardation. Nat Genet, 2009, 41(5): 535-543.
[82]	De Ligt J, Willemsen MH, Van Bon BWM, Kleefstra T, Yntema HG, Kroes T, Vulto-Van Silfhout AT, Koolen DA, De Vries P, Gilissen C, Del Rosario M, Hoischen A, Scheffer H, De Vries BB, Brunner HG, Veltman JA, Vissers LEL. Diagnostic exome sequencing in persons with severe intellectual disability. N Engl J Med, 2012, 367(20): 1921-1929.
[83]	Gandomi SK, Farwell Gonzalez KD, Parra M, Shahmirzadi L, Mancuso J, Pichurin P, Temme R, Dugan S, Zeng W, Tang S. Diagnostic exome sequencing identifies two novel IQSEC2 mutations associated with X-linked intellectual disability with seizures: implications for genetic counseling and clinical diagnosis. J Genet Couns, 2014, 23(3): 289-298.
[84]	Shoubridge C, Tarpey PS, Abidi F, Ramsden SL, Rujirabanjerd S, Murphy JA, Boyle J, Shaw M, Gardner A, Proos A, Puusepp H, Raymond FL, Schwartz CE, Stevenson RE, Turner G, Field M, Walikonis RS, Harvey RJ, Hackett A, Futreal PA, Stratton MR, Gécz J. Mutations in the guanine nucleotide exchange factor gene IQSEC2 cause nonsyndromic intellectual disability. Nat Genet, 2010, 42(6): 486-488.
[85]	Madrigal I, Alvarez-Mora MI, Rosell J, Rodríguez-Revenga L, Karlberg O, Sauer S, Syv?nen AC, Mila M. A novel splicing mutation in the IQSEC2 gene that modulates the phenotype severity in a family with intellectual disability. Eur J Hum Genet, 2016, 24(8): 1117-1123.
[86]	Koufaris C, Alexandrou A, Tanteles GA, Anastasiadou V, Sismani C. A novel HCFC1 variant in male siblings with intellectual disability and microcephaly in the absence of cobalamin disorder. Biomed Rep, 2016, 4(2): 215-218.
[87]	Fu LJ, Luo SS, Cai S, Hong WJ, Guo Y, Wu JJ, Liu TL, Zhao CB, Li F, Huang HM, Huang MR, Wang J. Identification of LAMP2 mutations in early-onset Danon disease with hypertrophic cardiomyopathy by targeted next-generation sequencing. Am J Cardiol, 2016, 118(6): 888-894.
[88]	Lahn BT, Page DC. Functional coherence of the human Y chromosome. Science, 1997, 278(5338): 675-680.
[89]	Cotton AM, Price EM, Jones MJ, Balaton BP, Kobor MS, Brown CJ. Landscape of DNA methylation on the X chromosome reflects CpG density, functional chromatin state and X-chromosome inactivation. Hum Mol Genet, 2015, 24(6): 1528-1539.
[90]	Solomon NM, Ross SA, Morgan T, Belsky JL, Hol FA, Karnes PS, Hopwood NJ, Myers SE, Tan AS, Warne GL, Forrest SM, Thomas PQ. Array comparative genomic hybridisation analysis of boys with X linked hypopituitarism identifies a 3.9 Mb duplicated critical region at Xq27 containing SOX3. J Med Genet, 2004, 41(9): 669-678.
[91]	Liu F, Song XZ, Xie H, Chen XL. The pathogenicity of somatic mutation to common tumors and developmentalmalformationof the nervous system. Hereditas (Beijing), 2016, 38(3): 196-205.
[91]	刘芳, 宋小珍, 谢华, 陈晓丽. 体细胞变异对神经系统常见肿瘤和发育异常类疾病的致病性. 遗传, 2016, 38(3): 196-205.
[92]	Luo SY, Huang W, Xia QP, Xia Y, Du Q, Wu LQ, Duan RH. Cryptic FMR1 mosaic deletion in a phenotypically normal mother of a boy with fragile X syndrome: case report. BMC Med Genet, 2014, 15(1): 125.
[93]	Chen XL, Wang JM, Xie H, Zhou WJ, Wu Y, Wang J, Qin J, Guo J, Gu Q, Zhang XZ, Ji TY, Zhang Y, Xiong ZM, Wang LW, Wu XR, Latham GJ, Jiang YW. Fragile X syndrome screening in Chinese children with unknown intellectual developmental disorder. BMC Pediatr, 2015, 15(1): 77.
[94]	Hurd PJ, Nelson CJ. Advantages of next-generation sequencing versus the microarray in epigenetic research. Brief Funct Genomics, 2009, 8(3): 174-183.
[95]	Su ZQ, Li ZG, Chen T, Li QZ, Fang H, Ding D, Ge WG, Ning BT, Hong HX, Perkins RG, Tong WD, Shi LM. Comparing next-generation sequencing and microarray technologies in a toxicological study of the effects of aristolochic acid on rat kidneys. Chem Res Toxicol, 2011, 24(9): 1486-1493.
[96]	Teo SM, Pawitan Y, Ku CS, Chia KS, Salim A. Statistical challenges associated with detecting copy number variations with next-generation sequencing. Bioinformatics, 2012, 28(21): 2711-2718.
[97]	Wang H, Nettleton D, Ying K. Copy number variation detection using next generation sequencing read counts. BMC Bioinform, 2014, 15(1): 109.
[98]	Jiang JC, Wang JY, Wang HF, Zhang Y, Kang HM, Feng XT, Wang JF, Yin ZJ, Bao WB, Zhang Q, Liu JF. Global copy number analyses by next generation sequencing provide insight into pig genome variation. BMC Genomics, 2014, 15(1): 593.
[99]	Fromer M, Moran JL, Chambert K, Banks E, Bergen SE, Ruderfer DM, Handsaker RE, McCarroll SA, O'Donovan MC, Owen MJ, Kirov G, Sullivan PF, Hultman CM, Sklar P, Purcell SM. Discovery and statistical genotyping of copy-number variation from whole-exome sequencing depth. Am J Hum Genet, 2012, 91(4): 597-607.
[100]	Ji TM, Chen J. Modeling the next generation sequencing read count data for DNA copy number variant study. Stat Appl Genet Mol Biol, 2015, 14(4): 361-374.

编辑推荐

Metrics

www.chinagene.cn
备案号：京ICP备09063187号-4
总访问:,今日访问:,当前在线:

X染色体变异对男性精神发育迟滞致病性的研究进展

The pathogenicity of genomic/genetic variant of X-chromosomal genes in males with intellectual disability

RichHTML

PDF (PC)

可视化

摘要/Abstract

引用本文

使用本文

参考文献

相关文章 6

编辑推荐

Metrics

[1]	刘静, 王亚楠, 孙亚奇, 王洪洋, 汪超, 彭中镇, 刘榜. 猪13号染色体上拷贝数变异区内基因信息发掘及遗传规律分析[J]. 遗传, 2014, 36(4): 354-359.
[2]	杜仁骞，金力，张锋. 基因组拷贝数变异及其突变机理与人类疾病[J]. 遗传, 2011, 33(8): 857-869.
[3]	李佩尧，贺福初，周钢桥. 人microRNA相关的遗传变异与肿瘤[J]. 遗传, 2011, 33(8): 870-878.
[4]	吴志俊，金玮. 拷贝数变异: 基因组多样性的新形式[J]. 遗传, 2009, 31(4): 339-347.
[5]	严卫丽. 复杂疾病全基因组关联研究进展—— 研究设计和遗传标记[J]. 遗传, 2008, 30(4): 400-406.
[6]	何阳花，俞英，张沅. 拷贝数变异与疾病的关系及其在动物抗病育种中的应用前景[J]. 遗传, 2008, 30(11): 1385-1391.