Co-existence of other copy number variations with 22q11.2 deletion or duplication: a modifier for variable phenotypes of the syndrome?

详细信息    查看全文

• 作者：Deling Li (1)
  Mustafa Tekin (2) (3)
  Maria Buch (4)
  Yao-Shan Fan (1)
  
• 关键词：DiGeorge syndrome ; 22q11.2 microdeletion ; 22q11.2 microduplication ; Array CGH ; Copy number variations (CNVs)
• 刊名：Molecular Cytogenetics
• 出版年：2012
• 出版时间：December 2012
• 年：2012
• 卷：5
• 期：1
• 全文大小：188KB
• 参考文献：1. McDonald-McGinn DM, Kirschner R, Goldmuntz E, Sullivan K, Eicher P, Gerdes M, Moss E, Solot C, Wang P, Jacobs I, Handler S, Knightly C, Heher K, Wilson M, Ming JE, Grace K, Driscoll D, Pasquariello P, Randall P, Larossa D, Emanuel BS, Zackai EH: The Philadelphia story: the 22q11.2 deletion: report on 250 patients. / Genet Couns 1999, 10:11鈥?4.
  2. Swillen A, Vogels A, Devriendt K, Fryns JP: Chromosome 22q11 deletion syndrome: update and review of the clinical features, cognitive-behavioral spectrum, and psychiatric complications. / Am J Med Genet 2000, 97:128鈥?35. CrossRef
  3. Emanuel BS, Budarf ML, Sellinger B, Goldmuntz E, Driscoll DA: Detection of microdeletions of 22q11.2 with fluorescence in situ hybridization (FISH): diagnosis of DiGeorge syndrome (DGS), velo-cardio facial (VCF) syndrome, CHARGE association and conotruncal cardiac malformations. / Am J Hum Genet 1992,51(Suppl):A3.
  4. Ensenauer RE, Adeyinka A, Flynn HC, Michels VV, Lindor NM, Dawson DB, Thorland EC, Lorentz CP, Goldstein JL, McDonald MT, Smith WE, Simon-Fayard E, Alexander AA, Kulharya AS, Ketterling RP, Clark RD, Jalal SM: Microduplication 22q11.2, an emerging syndrome: clinical, cytogenetic, and molecular analysis of thirteen patients. / Am J Hum Genet 2003, 73:1027鈥?040. CrossRef
  5. Cotter PD, Nguyen H, Tung G, Rauen KA: Incidence of microduplication 22q11.2 in patients referred for FISH testing for velo cardiofacial and DiGeorge syndromes. / Eur J Hum Genet 2005, 13:1245鈥?246. CrossRef
  6. Gothelf D, Frisch A, Michaelovsky E, Weizman A, Shprintzen RJ: Velo-cardio-facial syndrome. / J Ment Health Res Intellect Disabil 2009, 2:149鈥?67. CrossRef
  7. De La Rochebrochard C, Joly-H茅las G, Goldenberg A, Durand I, Laquerri猫re A, Ickowicz V, Saugier-Veber P, Eurin D, Moirot H, Diguet A, de Kergal F, Tiercin C, Mace B, Marpeau L, Frebourg T: The intrafamilial variability of the 22q11.2 microduplication encompasses a spectrum from minor cognitive deficits to severe congenital anomalies. / Am J Med Genet A 2006, 140:1608鈥?613.
  8. Ou Z, Berg JS, Yonath H, Enciso VB, Miller DT, Picker J, Lenzi T, Keegan CE, Sutton VR, Belmont J, Chinault AC, Lupski JR, Cheung SW, Roeder E, Patel A: Microduplications of 22q11.2 are frequently inherited and are associated with variable phenotypes. / Genet Med 2008, 10:267鈥?77. CrossRef
  9. Yagi H, Furutani Y, Hamada H, Sasaki T, Asakawa S, Minoshima S, Ichida F, Joo K, Kimura M, Imamura S, Kamatani N, Momma K, Takao A, Nakazawa M, Shimizu N, Matsuoka R: Role of TBX1 in human del22q11.2 syndrome. / Am J Med Genet 1999, 86:27鈥?3. CrossRef
  10. Rauch A, Zink S, Zweier C, Thiel CT, Koch A, Rauch R, Lascorz J, H眉ffmeier U, Weyand M, Singer H, Hofbeck M: Systematic assessment of atypical deletions reveals genotype-phenotype correlation in 22q11.2. / J Med Genet 2005, 42:871鈥?76. CrossRef
  11. Garcia-Mi帽aur S, Fantes J, Murray RS, Porteous ME, Strain L, Burns JE, Stephen J, Warner JP: A novel atypical 22q11.2 distal deletion in father and son. / J Med Genet 2002, 39:E62. CrossRef
  12. Kent L, Emerton J, Bhadravathi V, Weisblatt E, Pasco G, Willatt LR, McMahon R, Yates JR: X-linked ichthyosis (steroid sulfatase deficiency) is associated with increased risk of attention deficit hyperactivity disorder, autism and social communication deficits. / J Med Genet 2008, 45:519鈥?24. CrossRef
  13. Green T, Gothelf D, Glaser B, Debbane M, Frisch A, Kotler M, Weizman A, Eliez S: Psychiatric disorders and intellectual functioning throughout development in velocardiofacial (22q11.2 deletion) syndrome. / J Am Acad Child Adolesc Psychiatry 2009, 48:1060鈥?068. CrossRef
  14. Lo-Castro A, Galasso C, Cerminara C, El-Malhany N, Benedetti S, Nardone AM, Curatolo P: Association of syndromic mental retardation and autism with 22q11.2 duplication. / Neuropediatrics 2009, 40:137鈥?40. CrossRef
  15. Portno茂 MF: Microduplication 22q11.2: a new chromosomal syndrome. / Eur J Med Genet 2009, 52:88鈥?3. CrossRef
  16. Szafranski P, Schaaf CP, Person RE, Gibson IB, Xia Z, Mahadevan S, Wiszniewska J, Bacino CA, Lalani S, Potocki L, Kang SH, Patel A, Cheung SW, Probst FJ, Graham BH, Shinawi M, Beaudet AL, Stankiewicz P: Structures and molecular mechanisms for common 15q13.3 microduplications involving CHRNA7: benign or pathological? / Hum Mutat 2010, 31:840鈥?50. CrossRef
  17. Martin CL, Duvall JA, Ilkin Y, Simon JS, Arreaza MG, Wilkes K, Alvarez-Retuerto A, Whichello A, Powell CM, Rao K, Cook E, Geschwind DH: Cytogenetic and molecular characterization of A2BP1/FOX1 as a candidate gene for autism. / Am J Med Genet B 2007, 144B:869鈥?76. CrossRef
  18. Voineagu I, Wang X, Johnston P, Lowe JK, Tian Y, Horvath S, Mill J, Cantor RM, Blencowe BJ, Geschwind DH: Transcriptomic analysis of autistic brain reveals convergent molecular pathology. / Nature 2011, 474:380鈥?84. CrossRef
  19. Fan YS, Jayakar P, Zhu H, Barbouth D, Sacharow S, Morales A, Carver V, Benke P, Mundy P, Elsas LJ: Detection of pathogenic gene copy number variations in patients with mental retardationby genomewide oligonucleotide array comparative genomic hybridization. / Hum Mutat 2007, 28:1124鈥?132. CrossRef
  
• 作者单位：Deling Li (1)
  Mustafa Tekin (2) (3)
  Maria Buch (4)
  Yao-Shan Fan (1)
  
  1. Department of Pathology, University of Miami Miller School of Medicine, Miami, FL, 33136, USA
  2. Dr. John T. Macdonald Department of Human Genetics, University of Miami Miller School of Medicine, Miami, FL, 33136, USA
  3. John P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, FL, 33136, USA
  4. Jackson Memorial Hospital, University of Miami Miller School of Medicine, Miami, FL, 33136, USA
  
• ISSN：1755-8166

文摘

Background The phenotype in patients with a 22q11.2 deletion or duplication can be extremely variable, and the causes of such as variations are not well known. Results We observed additional copy number variations (CNVs) in 2 of 15 cases with a 22q11.2 deletion or duplication. Both cases were newborn babies referred for severe congenital heart defects. The first case had a deletion with a size of approximately 1.56 Mb involving multiple genes including STS in the Xp22.31 region along with a 22q11.2 deletion. The second case had a duplication of 605 kb in the 15q13.3 region encompassing CHRNA7 and a deletion of 209 kb involving the RBFOX1 gene in the 16p13.2 region, in addition to 22q11.2 duplication. Discussion Our observations have shown that additional CNVs are not rare (2/15, 13%) in patients with a 22q11.2 deletion or duplication. We speculate that these CNVs may contribute to phenotype variations of 22q11.2 microdeletion/duplication syndromes as genomic modifiers.