The evolving picture of microdeletion/microduplication syndromes in the age of microarray analysis: Variable expressivity and genomic complexity

Clinics in Laboratory Medicine

Volumn 31, Issue 4, 2011, Pages 543-564

  Deak, Kristen L ^a   Horn, Sarah R ^a   Rehder, Catherine W ^a  

^a DUKE UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

15q13; 15q24; 16p11.2; 16p13.1; 17q21.3; 1q21; Microarray; Microdeletion; Microduplication; Syndrome

Indexed keywords

ACP6 GENE; ALDOA GENE; ARHGAP11B GENE; ARID3B GENE; ASPHD1 GENE; BCL9 GENE; CDIPT1 GENE; CHD1L GENE; CHRNA7 GENE; CHROMOSOME 15; CHROMOSOME 15Q; CHROMOSOME 16; CHROMOSOME 1Q; CHROMOSOME ANALYSIS; CLINICAL FEATURE; CPLX3 GENE; CRHR1 GENE; CSK GENE; CYF1P1 GENE; CYP11A1 GENE; DIGEORGE SYNDROME; DOC2A GENE; FMO5 GENE; GENE; GENE DELETION; GENE DOSAGE; GENE DUPLICATION; GENE FREQUENCY; GENE INTERACTION; GENE LOCUS; GENE MUTATION; GENE REARRANGEMENT; GENE SEQUENCE; GENETIC ASSOCIATION; GENETIC PREDISPOSITION; GENETIC SUSCEPTIBILITY; GENOTYPE PHENOTYPE CORRELATION; GJA5 GENE; GJA8 GENE; GPR89B GENE; HAPPY PUPPET SYNDROME; HIRIP3 GENE; HOMOLOGOUS RECOMBINATION; HUMAN; IMP5 GENE; KCTD13 GENE; KIAA1267 GENE; KLF13 GENE; MAPK3 GENE; MAPT GENE; MAZ GENE; MICROARRAY ANALYSIS; MICROCEPHALY; MTMR10 GENE; MTMR15 GENE; MVP GENE; NDE1 GENE; NIPA1 GENE; NIPA2 GENE; NTAN1 GENE; OPEN READING FRAME; OTUD7A GENE; PHENOTYPE; PRADER WILLI SYNDROME; PRIORITY JOURNAL; PRKAB2 GENE; REVIEW; SEMA7A GENE; SEQUENCE HOMOLOGY; SEZ6L2 GENE; SH2B1 GENE; SIN3A GENE; SRTA6 GENE; STH GENE; SYNAPTIC TRANSMISSION; TBX6 GENE; THROMBOCYTOPENIA; TRPM1 GENE; TUBGCP5 GENE; WILLIAMS BEUREN SYNDROME;

CHROMOSOME ABERRATIONS; CHROMOSOME DISORDERS; CYTOGENETIC ANALYSIS; GENE DELETION; GENE DUPLICATION; HUMANS; OLIGONUCLEOTIDE ARRAY SEQUENCE ANALYSIS; SYNDROME;

EID: 82355181598     PISSN: 02722712     EISSN: 15579832     Source Type: Journal    
DOI: 10.1016/j.cll.2011.08.008     Document Type: Review

References (102)

1. Ledbetter D.H., Riccardi V.M., Airhart S.D., et al. Deletions of chromosome 15 as a cause of the Prader-Willi syndrome. N Engl J Med 1981, 304(6):325-329.
2. de la Chapelle A., Herva R., Koivisto M., et al. A deletion in chromosome 22 can cause DiGeorge syndrome. Hum Genet 1981, 57(3):253-256.
3. Morris C.A. Williams syndrome. GeneReviews 2006, NCBI Bookshelf, Seattle (WA). R.A. Pagon, T.D. Bird, C.R. Dolan (Eds.).
4. Cassidy S.B., Schwartz S. Prader-Willi syndrome. GeneReviews 2009, NCBI Bookshelf, Seattle (WA). R.A. Pagon, T.D. Bird, C.R. Dolan (Eds.).
5. Williams C.A., Dagli A.I., Driscoll D.J. Angelman syndrome. GeneReviews 2008, NCBI Bookshelf, Seattle (WA). R.A. Pagon, T.D. Bird, C.R. Dolan (Eds.).
6. McDonald-McGinn D.M., Emanuel B.S., Zackai E.H. 22q11.2 deletion syndrome. GeneReviews 2005, NCBI Bookshelf, Seattle (WA). R.A. Pagon, T.D. Bird, C.R. Dolan (Eds.).
7. Klopocki E., Schulze H., Strauss G., et al. Complex inheritance pattern resembling autosomal recessive inheritance involving a microdeletion in thrombocytopenia-absent radius syndrome. Am J Hum Genet 2007, 80(2):232-240.
8. Mefford H.C., Sharp A.J., Baker C., et al. Recurrent rearrangements of chromosome 1q21.1 and variable pediatric phenotypes. N Engl J Med 2008, 359(16):1685-1699.
9. Brunetti-Pierri N., Berg J.S., Scaglia F., et al. Recurrent reciprocal 1q21.1 deletions and duplications associated with microcephaly or macrocephaly and developmental and behavioral abnormalities. Nat Genet 2008, 40(12):1466-1471.
10. Doornbos M., Sikkema-Raddatz B., Ruijvenkamp C.A., et al. Nine patients with a microdeletion 15q11.2 between breakpoints 1 and 2 of the Prader-Willi critical region, possibly associated with behavioural disturbances. Eur J Med Genet 2009, 52(2-3):108-115.
11. Burnside R.D., Pasion R., Mikhail F.M., et al. Microdeletion/microduplication of proximal 15q11.2 between BP1 and BP2: a susceptibility region for neurological dysfunction including developmental and language delay. Hum Genet 2011, [Epub ahead of print].
12. Sharp A.J., Mefford H.C., Li K., et al. A recurrent 15q13.3 microdeletion syndrome associated with mental retardation and seizures. Nat Genet 2008, 40(3):322-328.
13. van Bon B.W., Mefford H.C., Menten B., et al. Further delineation of the 15q13 microdeletion and duplication syndromes: a clinical spectrum varying from non-pathogenic to a severe outcome. J Med Genet 2009, 46(8):511-523.
14. Helbig I., Mefford H.C., Sharp A.J., et al. 15q13.3 microdeletions increase risk of idiopathic generalized epilepsy. Nat Genet 2009, 41(2):160-162.
15. Miller D.T., Shen Y., Weiss L.A., et al. Microdeletion/duplication at 15q13.2q13.3 among individuals with features of autism and other neuropsychiatric disorders. J Med Genet 2009, 46(4):242-248.
16. Sharp A.J., Selzer R.R., Veltman J.A., et al. Characterization of a recurrent 15q24 microdeletion syndrome. Hum Mol Genet 2007, 16(5):567-572.
17. Klopocki E., Graul-Neumann L.M., Grieben U., et al. A further case of the recurrent 15q24 microdeletion syndrome, detected by array CGH. Eur J Pediatr 2008, 167(8):903-908.
18. Ullmann R., Turner G., Kirchhoff M., et al. Array CGH identifies reciprocal 16p13.1 duplications and deletions that predispose to autism and/or mental retardation. Hum Mutat 2007, 28(7):674-682.
19. Hannes F.D., Sharp A.J., Mefford H.C., et al. Recurrent reciprocal deletions and duplications of 16p13.11: the deletion is a risk factor for MR/MCA while the duplication may be a rare benign variant. J Med Genet 2009, 46(4):223-232.
20. Bochukova E.G., Huang N., Keogh J., et al. Large, rare chromosomal deletions associated with severe early-onset obesity. Nature 2010, 463(7281):666-670.
21. Bachmann-Gagescu R., Mefford H.C., Cowan C., et al. Recurrent 200-kb deletions of 16p11.2 that include the SH2B1 gene are associated with developmental delay and obesity. Genet Med 2010, 12(10):641-647.
22. Barge-Schaapveld D.Q., Maas S.M., Polstra A., et al. The atypical 16p11.2 deletion: a not so atypical microdeletion syndrome?. Am J Med Genet A 2011, 155(5):1066-1072.
23. Kumar R.A., KaraMohamed S., Sudi J., et al. Recurrent 16p11.2 microdeletions in autism. Hum Mol Genet 2008, 17(4):628-638.
24. Marshall C.R., Noor A., Vincent J.B., et al. Structural variation of chromosomes in autism spectrum disorder. Am J Hum Genet 2008, 82(2):477-488.
25. Weiss L.A., Shen Y., Korn J.M., et al. Association between microdeletion and microduplication at 16p11.2 and autism. N Engl J Med 2008, 358(7):667-675.
26. Miller D.T., Nasir R., Sobeih M.M., et al. 16p11.2 microdeletion. GeneReviews 2011, NCBI Bookshelf, Seattle (WA). R.A. Pagon, T.D. Bird, C.R. Dolan (Eds.).
27. Sharp A.J., Hansen S., Selzer R.R., et al. Discovery of previously unidentified genomic disorders from the duplication architecture of the human genome. Nat Genet 2006, 38(9):1038-1042.
28. Koolen D.A., Vissers L.E., Pfundt R., et al. A new chromosome 17q21.31 microdeletion syndrome associated with a common inversion polymorphism. Nat Genet 2006, 38(9):999-1001.
29. Shaw-Smith C., Pittman A.M., Willatt L., et al. Microdeletion encompassing MAPT at chromosome 17q21.3 is associated with developmental delay and learning disability. Nat Genet 2006, 38(9):1032-1037.
30. Koolen D.A., Sharp A.J., Hurst J.A., et al. Clinical and molecular delineation of the 17q21.31 microdeletion syndrome. J Med Genet 2008, 45(11):710-720.
31. Tan T.Y., Aftimos S., Worgan L., et al. Phenotypic expansion and further characterisation of the 17q21.31 microdeletion syndrome. J Med Genet 2009, 46(7):480-489.
32. Slavotinek A.M. Novel microdeletion syndromes detected by chromosome microarrays. Hum Genet 2008, 124(1):1-17.
33. Girirajan S., Eichler E.E. Phenotypic variability and genetic susceptibility to genomic disorders. Hum Mol Genet 2010, 19(R2):R176-R187.
34. Girirajan S., Rosenfeld J.A., Cooper G.M., et al. A recurrent 16p12.1 microdeletion supports a two-hit model for severe developmental delay. Nat Genet 2010, 42(3):203-209.
35. Velinov M., Dolzhanskaya N. Clavicular pseudoarthrosis, anomalous coronary artery and extra crease of the fifth finger-previously unreported features in individuals with class II 1q21.1 microdeletions. Eur J Med Genet 2010, 53(4):213-216.
36. Brunet A., Armengol L., Heine D., et al. BAC array CGH in patients with Velocardiofacial syndrome-like features reveals genomic aberrations on chromosome region 1q21.1. BMC Med Genet 2009, 10:144.
37. Chung C.D., Liao J., Liu B., et al. Specific inhibition of Stat3 signal transduction by PIAS3. Science 1997, 278(5344):1803-1805.
38. Swindell E.C., Moeller C., Thaller C., et al. Cloning and expression analysis of chicken Lix1, a founding member of a novel gene family. Mech Dev 2001, 109(2):405-408.
39. Stefansson H., Rujescu D., Cichon S., et al. Large recurrent microdeletions associated with schizophrenia. Nature 2008, 455(7210):232-236.
40. Christiansen J., Dyck J.D., Elyas B.G., et al. Chromosome 1q21.1 contiguous gene deletion is associated with congenital heart disease. Circ Res 2004, 94(11):1429-1435.
41. Gollob M.H. Cardiac connexins as candidate genes for idiopathic atrial fibrillation. Curr Opin Cardiol 2006, 21(3):155-158.
42. Shiels A., Mackay D., Ionides A., et al. A missense mutation in the human connexin50 gene (GJA8) underlies autosomal dominant "zonular pulverulent" cataract, on chromosome 1q. Am J Hum Genet 1998, 62(3):526-532.
43. Willoughby C.E., Arab S., Gandhi R., et al. A novel GJA8 mutation in an Iranian family with progressive autosomal dominant congenital nuclear cataract. J Med Genet 2003, 40(11):e124.
44. Devi R.R., Vijayalakshmi P. Novel mutations in GJA8 associated with autosomal dominant congenital cataract and microcornea. Mol Vis 2006, 12:190-195.
45. Arora A., Minogue P.J., Liu X., et al. A novel connexin50 mutation associated with congenital nuclear pulverulent cataracts. J Med Genet 2008, 45(3):155-160.
46. Kumar M., Agarwal T., Khokhar S., et al. Mutation screening and genotype phenotype correlation of alpha-crystallin, gamma-crystallin and GJA8 gene in congenital cataract. Mol Vis 2011, 17:693-707.
47. Li J., Zhou G., Ji W., et al. Common variants in the BCL9 gene conferring risk of schizophrenia. Arch Gen Psychiatry 2011, 68(3):232-240.
48. Dumas L., Sikela J.M. DUF1220 domains, cognitive disease, and human brain evolution. Cold Spring Harb Symp Quant Biol 2009, 74:375-382.
49. Freedman R., Coon H., Myles-Worsley M., et al. Linkage of a neurophysiological deficit in schizophrenia to a chromosome 15 locus. Proc Natl Acad Sci USA 1997, 94(2):587-592.
50. Elmslie F.V., Rees M., Williamson M.P., et al. Genetic mapping of a major susceptibility locus for juvenile myoclonic epilepsy on chromosome 15q. Hum Mol Genet 1997, 6(8):1329-1334.
51. Orr-Urtreger A., Goldner F.M., Saeki M., et al. Mice deficient in the alpha7 neuronal nicotinic acetylcholine receptor lack alpha-bungarotoxin binding sites and hippocampal fast nicotinic currents. J Neurosci 1997, 17(23):9165-9171.
52. Szafranski P., Schaaf C.P., Person R.E., et al. Structures and molecular mechanisms for common 15q13.3 microduplications involving CHRNA7: benign or pathological?. Hum Mutat 2010, 31(7):840-850.
53. Rosenfeld J.A., Stephens L.E., Coppinger J., et al. Deletions flanked by breakpoints 3 and 4 on 15q13 may contribute to abnormal phenotypes. Eur J Hum Genet 2011, 19(5):547-554.
54. Sahoo T., Bacino C.A., German J.R., et al. Identification of novel deletions of 15q11q13 in Angelman syndrome by array-CGH: molecular characterization and genotype-phenotype correlations. Eur J Hum Genet 2007, 15(9):943-949.
55. Bittel D.C., Kibiryeva N., Butler M.G. Expression of 4 genes between chromosome 15 breakpoints 1 and 2 and behavioral outcomes in Prader-Willi syndrome. Pediatrics 2006, 118(4):e1276-e1283.
56. Chai J.H., Locke D.P., Greally J.M., et al. Identification of four highly conserved genes between breakpoint hotspots BP1 and BP2 of the Prader-Willi/Angelman syndromes deletion region that have undergone evolutionary transposition mediated by flanking duplicons. Am J Hum Genet 2003, 73(4):898-925.
57. de Kovel C.G., Trucks H., Helbig I., et al. Recurrent microdeletions at 15q11.2 and 16p13.11 predispose to idiopathic generalized epilepsies. Brain 2010, 133(Pt 1):23-32.
58. El-Hattab A.W., Smolarek T.A., Walker M.E., et al. Redefined genomic architecture in 15q24 directed by patient deletion/duplication breakpoint mapping. Hum Genet 2009, 126(4):589-602.
59. Van Esch H., Backx L., Pijkels E., et al. Congenital diaphragmatic hernia is part of the new 15q24 microdeletion syndrome. Eur J Med Genet 2009, 52(2-3):153-156.
60. Masurel-Paulet A., Callier P., Thauvin-Robinet C., et al. Multiple cysts of the corpus callosum and psychomotor delay in a patient with a 3.1 Mb 15q24.1q24.2 interstitial deletion identified by array-CGH. Am J Med Genet A 2009, 149A(7):1504-1510.
61. Andrieux J., Dubourg C., Rio M., et al. Genotype-phenotype correlation in four 15q24 deleted patients identified by array-CGH. Am J Med Genet A 2009, 149A(12):2813-2819.
62. Kiholm Lund A.B., Hove H.D., Kirchhoff M. A 15q24 microduplication, reciprocal to the recently described 15q24 microdeletion, in a boy sharing clinical features with 15q24 microdeletion syndrome patients. Eur J Med Genet 2008, 51(6):520-526.
63. Cukier H.N., Salyakina D., Blankstein S.F., et al. Microduplications in an autism multiplex family narrow the region of susceptibility for developmental disorders on 15q24 and implicate 7p21. Am J Med Genet B Neuropsychiatr Genet 2011, 156(4):493-501.
64. Roetzer K.M., Schwarzbraun T., Obenauf A.C., et al. Further evidence for the pathogenicity of 15q24 microduplications distal to the minimal critical regions. Am J Med Genet A 2010, 152A(12):3173-3178.
65. Bailey J.A., Gu Z., Clark R.A., et al. Recent segmental duplications in the human genome. Science 2002, 297(5583):1003-1007.
66. Martin J., Han C., Gordon L.A., et al. The sequence and analysis of duplication-rich human chromosome 16. Nature 2004, 432(7020):988-994.
67. Nagamani S.C., Erez A., Bader P., et al. Phenotypic manifestations of copy number variation in chromosome 16p13.11. Eur J Hum Genet 2011, 19(3):280-286.
68. Balasubramanian M., Smith K., Mordekar S.R., et al. Clinical report: An interstitial deletion of 16p13.11 detected by array CGH in a patient with infantile spasms. Eur J Med Genet 2011, 54(3):314-318.
69. Heinzen E.L., Radtke R.A., Urban T.J., et al. Rare deletions at 16p13.11 predispose to a diverse spectrum of sporadic epilepsy syndromes. Am J Hum Genet 2010, 86(5):707-718.
70. Mefford H.C., Muhle H., Ostertag P., et al. Genome-wide copy number variation in epilepsy: novel susceptibility loci in idiopathic generalized and focal epilepsies. PLoS Genet 2010, 6(5). e1000962.
71. Kirov G., Grozeva D., Norton N., et al. Support for the involvement of large copy number variants in the pathogenesis of schizophrenia. Hum Mol Genet 2009, 18(8):1497-1503.
72. Ingason A., Rujescu D., Cichon S., et al. Copy number variations of chromosome 16p13.1 region associated with schizophrenia. Mol Psychiatry 2011, 16(1):17-25.
73. Feng Y., Walsh C.A. Mitotic spindle regulation by Nde1 controls cerebral cortical size. Neuron 2004, 44(2):279-293.
74. Pawlisz A.S., Mutch C., Wynshaw-Boris A., et al. Lis1-Nde1-dependent neuronal fate control determines cerebral cortical size and lamination. Hum Mol Genet 2008, 17(16):2441-2455.
75. Kim S., Zaghloul N.A., Bubenshchikova E., et al. Nde1-mediated inhibition of ciliogenesis affects cell cycle re-entry. Nat Cell Biol 2011, 13(4):351-360.
76. Alkuraya F.S., Cai X., Emery C., et al. Human mutations in NDE1 cause extreme microcephaly with lissencephaly. Am J Hum Genet 2011, 88(5):536-547.
77. Bakircioglu M., Carvalho O.P., Khurshid M., et al. The essential role of centrosomal NDE1 in human cerebral cortex neurogenesis. Am J Hum Genet 2011, 88(5):523-535.
78. Kwon Y.T., Balogh S.A., Davydov I.V., et al. Altered activity, social behavior, and spatial memory in mice lacking the NTAN1p amidase and the asparagine branch of the N-end rule pathway. Mol Cell Biol 2000, 20(11):4135-4148.
79. Ballif B.C., Hornor S.A., Jenkins E., et al. Discovery of a previously unrecognized microdeletion syndrome of 16p11.2-p12.2. Nat Genet 2007, 39(9):1071-1073.
80. Battaglia A., Novelli A., Bernardini L., et al. Further characterization of the new microdeletion syndrome of 16p11.2-p12.2. Am J Med Genet A 2009, 149A(6):1200-1204.
81. Bijlsma E.K., Gijsbers A.C., Schuurs-Hoeijmakers J.H., et al. Extending the phenotype of recurrent rearrangements of 16p11.2: deletions in mentally retarded patients without autism and in normal individuals. Eur J Med Genet 2009, 52(2-3):77-87.
82. Firth H.V., Richards S.M., Bevan A.P., et al. DECIPHER: Database of Chromosomal Imbalance and Phenotype in Humans Using Ensembl Resources. Am J Hum Genet 2009, 84(4):524-533.
83. Sampson M.G., Coughlin C.R., Kaplan P., et al. Evidence for a recurrent microdeletion at chromosome 16p11.2 associated with congenital anomalies of the kidney and urinary tract (CAKUT) and Hirschsprung disease. Am J Med Genet A 2010, 152A(10):2618-2622.
84. Ren D., Zhou Y., Morris D., et al. Neuronal SH2B1 is essential for controlling energy and glucose homeostasis. J Clin Invest 2007, 117(2):397-406.
85. Sebat J., Lakshmi B., Malhotra D., et al. Strong association of de novo copy number mutations with autism. Science 2007, 316(5823):445-449.
86. Ghebranious N., Giampietro P.F., Wesbrook F.P., et al. A novel microdeletion at 16p11.2 harbors candidate genes for aortic valve development, seizure disorder, and mild mental retardation. Am J Med Genet A 2007, 143A(13):1462-1471.
87. Fernandez B.A., Roberts W., Chung B., et al. Phenotypic spectrum associated with de novo and inherited deletions and duplications at 16p11.2 in individuals ascertained for diagnosis of autism spectrum disorder. J Med Genet 2010, 47(3):195-203.
88. McCarthy S.E., Makarov V., Kirov G., et al. Microduplications of 16p11.2 are associated with schizophrenia. Nat Genet 2009, 41(11):1223-1227.
89. Kumar R.A., Marshall C.R., Badner J.A., et al. Association and mutation analyses of 16p11.2 autism candidate genes. PLoS One 2009, 4(2):e4582.
90. Crepel A., Steyaert J., De la Marche W., et al. Narrowing the critical deletion region for autism spectrum disorders on 16p11.2. Am J Med Genet B Neuropsychiatr Genet 2011, 156(2):243-245.
91. Glessner J.T., Wang K., Cai G., et al. Autism genome-wide copy number variation reveals ubiquitin and neuronal genes. Nature 2009, 459(7246):569-573.
92. Grisart B., Willatt L., Destree A., et al. 17q21.31 microduplication patients are characterised by behavioural problems and poor social interaction. J Med Genet 2009, 46(8):524-530.
93. Kirchhoff M., Bisgaard A.M., Duno M., et al. A 17q21.31 microduplication, reciprocal to the newly described 17q21.31 microdeletion, in a girl with severe psychomotor developmental delay and dysmorphic craniofacial features. Eur J Med Genet 2007, 50(4):256-263.
94. Stefansson H., Helgason A., Thorleifsson G., et al. A common inversion under selection in Europeans. Nat Genet 2005, 37(2):129-137.
95. Rao P.N., Li W., Vissers L.E., et al. Recurrent inversion events at 17q21.31 microdeletion locus are linked to the MAPT H2 haplotype. Cytogenet Genome Res 2010, 129(4):275-279.
96. Shimokawa O., Kurosawa K., Ida T., et al. Molecular characterization of inv dup del(8p): analysis of five cases. Am J Med Genet A 2004, 128A(2):133-137.
97. Bayes M., Magano L.F., Rivera N., et al. Mutational mechanisms of Williams-Beuren syndrome deletions. Am J Hum Genet 2003, 73(1):131-151.
98. De Souza E.B. Corticotropin-releasing factor receptors: physiology, pharmacology, biochemistry and role in central nervous system and immune disorders. Psychoneuroendocrinology 1995, 20(8):789-819.
99. Smith G.W., Aubry J.M., Dellu F., et al. Corticotropin releasing factor receptor 1-deficient mice display decreased anxiety, impaired stress response, and aberrant neuroendocrine development. Neuron 1998, 20(6):1093-1102.
100. Ikegami S., Harada A., Hirokawa N. Muscle weakness, hyperactivity, and impairment in fear conditioning in tau-deficient mice. Neurosci Lett 2000, 279(3):129-132.
101. Takei Y., Teng J., Harada A., et al. Defects in axonal elongation and neuronal migration in mice with disrupted tau and map1b genes. J Cell Biol 2000, 150(5):989-1000.
102. Cooper G.M., Coe B.P., Girirajan S., et al. A copy number variation morbidity map of developmental delay. Nat Genet 2011, 43(9):838-846.