Diagnosis of Cryptic Chromosomal Syndromes by Fluorescence In Situ Hybridization (FISH)

Catherine D. Kashork1, Aaron Theisen1, Lisa G. Shaffer1

1 Signature Genomic Laboratories, Spokane, Washington
Publication Name:  Current Protocols in Human Genetics
Unit Number:  Unit 8.10
DOI:  10.1002/0471142905.hg0810s67
Online Posting Date:  October, 2010
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This unit describes the various methods by which cytogeneticists detect chromosome abnormalities. The unit offers guidance for detecting such abnormalities with fluorescence in situ hybridization (FISH), as well as the benefits, limitations, and other applications of FISH. Curr. Protoc. Hum. Genet. 67:8.10.1‐8.10.20 © 2010 by John Wiley & Sons, Inc.

Keywords: FISH; cytogenetics; chromosomal abnormalities

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Table of Contents

  • Introduction
  • Probes for FISH
  • FISH in the Clinical Setting
  • Literature Cited
  • Tables
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Literature Cited

Literature Cited
   NIH/IMMED. 1996. A complete set of human telomeric probes and their clinical application. National Institutes of Health and Institute of Molecular Medicine collaboration. Nat. Genet. 14:86‐89.
   Ahn, J., Ludecke, H.J., Lindow, S., Horton, W.A., Lee, B., Wagner, M.J., Horsthemke, B., and Wells, D.E. 1995. Cloning of the putative tumour suppressor gene for hereditary multiple exostoses (EXT1). Nat. Genet. 11:137‐143.
   Alberti, A., Romano, C., Falco, M., Cali, F., Schinocca, P., Galesi, O., Spalletta, A., Di Benedetto, D., and Fichera, M. 2007. 1.5 Mb de novo 22q11.21 microduplication in a patient with cognitive deficits and dysmorphic facial features. Clin. Genet. 71:177‐182.
   Altherr, M.R., Bengtsson, U., Elder, F.F., Ledbetter, D.H., Wasmuth, J.J., McDonald, M.E., Gusella, J.F., and Greenberg, F. 1991. Molecular confirmation of Wolf‐Hirschhorn syndrome with a subtle translocation of chromosome 4. Am. J. Hum. Genet. 49:1235‐1242.
   Altherr, M.R., Wright, T.J., Denison, K., Perez‐Castro, A.V., and Johnson, V.P. 1997. Delimiting the Wolf‐Hirschhorn syndrome critical region to 750 kilobase pairs. Am. J. Med. Genet. 71:47‐53.
   Anderlid, B.M., Schoumans, J., Anneren, G., Tapia‐Paez, I., Dumanski, J., Blennow, E., and Nordenskjold, M. 2002. FISH‐mapping of a 100‐kb terminal 22q13 deletion. Hum. Genet. 110:439‐443.
   Ballabio, A., Parenti, G., Tippett, P., Mondello, C., Di Maio, S., Tenore, A., and Andria, G. 1986. X‐linked ichthyosis, due to steroid sulphatase deficiency, associated with Kallmann syndrome (hypogonadotropic hypogonadism and anosmia): Linkage relationships with Xg and cloned DNA sequences from the distal short arm of the X chromosome. Hum. Genet. 72:237‐240.
   Ballabio, A., Carrozzo, R., Parenti, G., Gil, A., Zollo, M., Persico, M.G., Gillard, E., Affara, N., Yates, J., Ferguson‐Smith, M.A., Frants, R.R., Eriksson, A.W., and Andria, G. 1989. Molecular heterogeneity of steroid sulfatase deficiency: a multicenter study on 57 unrelated patients, at DNA and protein levels. Genomics 4:36‐40.
   Bartsch, O., Rasi, S., Hoffmann, K., and Blin, N. 2005. FISH of supernumerary marker chromosomes (SMCs) identifies six diagnostically relevant intervals on chromosome 22q and a novel type of bisatellited SMC(22). Eur. J. Hum. Genet. 13:592‐598.
   Battaglia, A., Carey, J.C., and Wright, T.J. 2001. Wolf‐Hirschhorn (4p‐) syndrome. Adv. Pediatr. 48:75‐113.
   Ben‐Shachar, S., Ou, Z., Shaw, C.A., Belmont, J.W., Patel, M.S., Hummel, M., Amato, S., Tartaglia, N., Berg, J., Sutton, V.R., Lalani, S.R., Chinault, A.C., Cheung, S.W., Lupski, J.R., and Patel, A. 2008. 22q11.2 distal deletion: A recurrent genomic disorder distinct from DiGeorge syndrome and velocardiofacial syndrome. Am. J. Hum. Genet. 82:214‐221.
   Berend, S.A., Spikes, A.S., Kashork, C.D., Wu, J.M., Daw, S.C., Scambler, P.J., and Shaffer, L.G. 2000. Dual‐probe fluorescence in situ hybridization assay for detecting deletions associated with VCFS/DiGeorge syndrome I and DiGeorge syndrome II loci. Am. J. Med. Genet. 91:313‐317.
   Berg, J.S., Brunetti‐Pierri, N., Peters, S.U., Kang, S.H., Fong, C.T., Salamone, J., Freedenberg, D., Hannig, V.L., Prock, L.A., Miller, D.T., Raffalli, P., Harris, D.J., Erickson, R.P., Cunniff, C., Clark, G.D., Blazo, M.A., Peiffer, D.A., Gunderson, K.L., Sahoo, T., Patel, A., Lupski, J.R., Beaudet, A.L., and Cheung, S.W. 2007. Speech delay and autism spectrum behaviors are frequently associated with duplication of the 7q11.23 Williams‐Beuren syndrome region. Genet. Med. 9:427‐441.
   Blair, I.P., Nash, J., Gordon, M.J., and Nicholson, G.A. 1996. Prevalence and origin of de novo duplications in Charcot‐Marie‐Tooth disease type 1A: First report of a de novo duplication with a maternal origin. Am. J. Hum. Genet. 58:472‐476.
   Bovolenta, M., Neri, M., Fini, S., Fabris, M., Trabanelli, C., Venturoli, A., Martoni, E., Bassi, E., Spitali, P., Brioschi, S., Falzarano, M.S., Rimessi, P., Ciccone, R., Ashton, E., McCauley, J., Yau, S., Abbs, S., Muntoni, F., Merlini, L., Gualandi, F., and Ferlini, A. 2008. A novel custom high density‐comparative genomic hybridization array detects common rearrangements as well as deep intronic mutations in dystrophinopathies. BMC Genomics 9:572.
   Breuning, M.H., Dauwerse, H.G., Fugazza, G., Saris, J.J., Spruit, L., Wijnen, H., Tommerup, N., van der Hagen, C.B., Imaizumi, K., Kuroki, Y., van den Boogaard, M.J., de Pater, J.M., Mariman, E.C., Hamel, B.C., Himmelbauer, H., Frischauf, A.M., Stallings, R., Beverstock, G.C., van Ommen, G.J., and Hennekam, R.C. 1993. Rubinstein‐Taybi syndrome caused by submicroscopic deletions within 16p13.3. Am. J. Hum. Genet. 52:249‐254.
   Brewer, C., Holloway, S., Zawalnyski, P., Schinzel, A., FitzPatrick, D. 1998. A chromosomal deletion map of human malformations. Am. J. Hum. Genet. 63:1153‐1159.
   Brewer, C., Holloway, S., Zawalnyski, P., Schinzel, A., and FitzPatrick, D. 1999. A chromosomal duplication map of malformations: Regions of suspected haplo‐ and triplolethality–and tolerance of segmental aneuploidy–in humans. Am. J. Hum. Genet. 64:1702‐1708.
   Carter, C.O., Hamerton, J.L., Polani, P.E., Gunalp, A., and Weller, S.D. 1960. Chromosome translocation as a cause of familial mongolism. Lancet 2:678‐680.
   Caspersson, T., Lomakka, G., and Zech, L. 1972. The 24 fluorescence patterns of the human metaphase chromosomes: Distinguishing characters and variability. Hereditas 67:89‐102.
   Church, D.M., Yang, J., Bocian, M., Shiang, R., and Wasmuth, J.J. 1997. A high‐resolution physical and transcript map of the Cri du chat region of human chromosome 5p. Genome Res. 7:787‐801.
   Cnossen, M.H., van der Est, M.N., Breuning, M.H., van Asperen, C.J., Breslau‐Siderius, E.J., van der Ploeg, A.T., de Goede‐Bolder, A., van den Ouweland, A.M., Halley, D.J., and Niermeijer, M.F. 1997. Deletions spanning the neurofibromatosis type 1 gene: Implications for genotype‐phenotype correlations in neurofibromatosis type 1? Hum. Mutat. 9:458‐464.
   Conary, J.T., Lorkowski, G., Schmidt, B., Pohlmann, R., Nagel, G., Meyer, H.E., Krentler, C., Cully, J., Hasilik, A., and von Figura, K. 1987. Genetic heterogeneity of steroid sulfatase deficiency revealed with cDNA for human steroid sulfatase. Biochem. Biophys. Res. Commun. 144:1010‐1017.
   Cook, E.H. Jr., Lindgren, V., Leventhal, B.L., Courchesne, R., Lincoln, A., Shulman, C., Lord, C., and Courchesne, E. 1997. Autism or atypical autism in maternally but not paternally derived proximal 15q duplication. Am. J. Hum. Genet. 60:928‐934.
   Cowell, J.K., Hungerford, J., Rutland, P., and Jay, M. 1989. Genetic and cytogenetic analysis of patients showing reduced esterase‐D levels and mental retardation from a survey of 500 individuals with retinoblastoma. Ophthalmic Paediatr. Genet. 10:117‐127.
   Crolla, J.A. and van Heyningen, V. 2002. Frequent chromosome aberrations revealed by molecular cytogenetic studies in patients with aniridia. Am. J. Hum. Genet. 71:1138‐1149.
   Delach, J.A., Rosengren, S.S., Kaplan, L., Greenstein, R.M., Cassidy, S.B., and Benn, P.A. 1994. Comparison of high resolution chromosome banding and fluorescence in situ hybridization (FISH) for the laboratory evaluation of Prader‐Willi syndrome and Angelman syndrome. Am. J. Med. Genet. 52:85‐91.
   de la Chapelle, A., Herva, R., Koivisto, M., and Aula, P. 1981. A deletion in chromosome 22 can cause DiGeorge syndrome. Hum. Genet. 57:253‐256.
   del Gaudio, D., Yang, Y., Boggs, B.A., Schmitt, E.S., Lee, J.A., Sahoo, T., Pham, H.T., Wiszniewska, J., Chinault, A.C., Beaudet, A.L., and Eng, C.M. 2008. Molecular diagnosis of Duchenne/Becker muscular dystrophy: Enhanced detection of dystrophin gene rearrangements by oligonucleotide array‐comparative genomic hybridization. Hum. Mutat. 29:1100‐1107.
   Devriendt, K., Fryns, J.P., Mortier, G., van Thienen, M.N., and Keymolen, K. 1998. The annual incidence of DiGeorge/velocardiofacial syndrome. J. Med. Genet. 35:789‐790.
   Dobyns, W.B., Curry, C.J., Hoyme, H.E., Turlington, L., and Ledbetter, D.H. 1991. Clinical and molecular diagnosis of Miller‐Dieker syndrome. Am. J. Hum. Genet. 48:584‐594.
   Dobyns, W.B., Reiner, O., Carrozzo, R., and Ledbetter, D.H. 1993. Lissencephaly: A human brain malformation associated with deletion of the LIS1 gene located at chromosome 17p13. JAMA 270:2838‐2842.
   Driscoll, D.A., Spinner, N.B., Budarf, M.L., McDonald‐McGinn, D.M., Zackai, E.H., Goldberg, R.B., Shprintzen, R.J., Saal, H.M., Zonana, J., Jones, M.C., Mascarello, J.T., and Emanuel, B.S. 1992a. Deletions and microdeletions of 22q11.2 in velo‐cardio‐facial syndrome. Am. J. Med. Genet. 44:261‐268.
   Driscoll, D.J., Waters, M.F., Williams, C.A., Zori, R.T., Glenn, C.C., Avidano, K.M., and Nicholls, R.D. 1992b. A DNA methylation imprint, determined by the sex of the parent, distinguishes the Angelman and Prader‐Willi syndromes. Genomics 13:917‐924.
   Ensenauer, R.E., Adeyinka, A., Flynn, H.C., Michels, V.V., Lindor, N.M., Dawson, D.B., Thorland, E.C., Lorentz, C.P., Goldstein, J.L., McDonald, M.T., Smith, W.E., Simon‐Fayard, E., Alexander, A.A., Kulharya, A.S., Ketterling, R.P., Clark, R.D., and Jalal, S.M. 2003. Microduplication 22q11.2, an emerging syndrome: Clinical, cytogenetic, and molecular analysis of thirteen patients. Am. J. Hum. Genet. 73:1027‐1040.
   Ewart, A.K., Morris, C.A., Atkinson, D., Jin, W., Sternes, K., Spallone, P., Stock, A.D., Leppert, M., and Keating, M.T. 1993. Hemizygosity at the elastin locus in a developmental disorder, Williams syndrome. Nat. Genet. 5:11‐16.
   Ferrero, G.B., Gebbia, M., Pilia, G., Witte, D., Peier, A., Hopkin, R.J., Craigen, W.J., Shaffer, L.G., Schlessinger, D., Ballabio, A., and Casey, B. 1997. A submicroscopic deletion in Xq26 associated with familial situs ambiguus. Am. J. Hum. Genet. 61:395‐401.
   Flint, J., Wilkie, A.O., Buckle, V.J., Winter, R.M., Holland, A.J., and McDermid, H.E. 1995. The detection of subtelomeric chromosomal rearrangements in idiopathic mental retardation. Nat. Genet. 9:132‐140.
   Greenberg, F., Guzzetta, V., Montes de Oca‐Luna, R., Magenis, R.E., Smith, A.C., Richter, S.F., Kondo, I., Dobyns, W.B., Patel, P.I., and Lupski, J.R. 1991. Molecular analysis of the Smith‐Magenis syndrome: A possible contiguous‐gene syndrome associated with del(17)(p11.2). Am. J. Hum. Genet. 49:1207‐1218.
   Guo, W., Mason, J.S., Stone, C.G. Jr., Morgan, S.A., Madu, S.I., Baldini, A., Lindsay, E.A., Biesecker, L.G., Copeland, K.C., Horlick, M.N., Pettigrew, A.L., Zanaria, E., and McCabe, E.R.B. 1995. Diagnosis of X‐linked adrenal hypoplasia congenita by mutation analysis of the DAX1 gene. JAMA 274:324‐330.
   Hardelin, J.P., Levilliers, J., Young, J., Pholsena, M., Legouis, R., Kirk, J., Bouloux, P., Petit, C., and Schaison, G. 1993. Xp22.3 deletions in isolated familial Kallmann's syndrome. J. Clin. Endocrinol. Metab. 76:827‐831.
   Hassed, S.J., Hopcus‐Niccum, D., Zhang, L., Li, S., and Mulvihill, J.J. 2004. A new genomic duplication syndrome complementary to the velocardiofacial (22q11 deletion) syndrome. Clin. Genet. 65:400‐404.
   Heilstedt, H.A., Ballif, B.C., Howard, L.A., Kashork, C.D., and Shaffer, L.G. 2003a. Population data suggest that deletions of 1p36 are a relatively common chromosome abnormality. Clin. Genet. 64:310‐316.
   Heilstedt, H.A., Ballif, B.C., Howard, L.A., Lewis, R.A., Stal, S., Kashork, C.D., Bacino, C.A., Shapira, S.K., and Shaffer, L.G. 2003b. Physical map of 1p36, placement of breakpoints in monosomy 1p36, and clinical characterization of the syndrome. Am. J. Hum. Genet. 72:1200‐1212.
   Henry, I., Puech, A., Riesewijk, A., Ahnine, L., Mannens, M., Beldjord, C., Bitoun, P., Tournade, M.F., Landrieu, P., and Junien, C. 1993. Somatic mosaicism for partial paternal isodisomy in Wiedemann‐Beckwith syndrome: A post‐fertilization event. Eur. J. Hum. Genet. 1:19‐29.
   Inoue, K., Osaka, H., Imaizumi, K., Nezu, A., Takanashi, J., Arii, J., Murayama, K., Ono, J., Kikawa, Y., Mito, T., Shaffer, L.G., and Lupski, J.R. 1999. Proteolipid protein gene duplications causing Pelizaeus‐Merzbacher disease: Molecular mechanism and phenotypic manifestations. Ann. Neurol. 45:624‐632.
   Inoue, K., Dewar, K., Katsanis, N., Reiter, L.T., Lander, E.S., Devon, K.L., Wyman, D.W., Lupski, J.R., and Birren, B. 2001. The 1.4‐Mb CMT1A duplication/HNPP deletion genomic region reveals unique genome architectural features and provides insights into the recent evolution of new genes. Genome Res. 11:1018‐1033.
   Jauch, A., Daumer, C., Lichter, P., Murken, J., Schroeder‐Kurth, T., and Cremer, T. 1990. Chromosomal in situ suppression hybridization of human gonosomes and autosomes and its use in clinical cytogenetics. Hum. Genet. 85:145‐150.
   Johnson, A., Minoshima, S., Asakawa, S., Shimizu, N., Shizuya, H., Roe, B.A., and McDermid, H.E. 1999. A 1.5‐Mb contig within the cat eye syndrome critical region at human chromosome 22q11.2. Genomics 57:306‐309.
   Johnston, J.J., Olivos‐Glander, I., Turner, J., Aleck, K., Bird, L.M., Mehta, L., Schimke, R.N., Heilstedt, H., Spence, J.E., Blancato, J., and Biesecker, L.G. 2003. Clinical and molecular delineation of the Greig cephalopolysyndactyly contiguous gene deletion syndrome and its distinction from acrocallosal syndrome. Am. J. Med. Genet. A 123A:236‐242.
   Kashork, C.D., Sutton, V.R., Fonda Allen, J.S., Schmidt, D.E., Likhite, M.L., Potocki, L., O'Brien, W.E., and Shaffer, L.G. 2002. Low or absent unconjugated estriol in pregnancy: An indicator for steroid sulfatase deficiency detectable by fluorescence in situ hybridization and biochemical analysis. Prenat. Diagn. 22:1028‐1032.
   Kayserili, H., Cox, T.C., Cox, L.L., Basaran, S., Kilic, G., Ballabio, A., and Yuksel‐Apak, M. 2001. Molecular characterisation of a new case of microphthalmia with linear skin defects (MLS). J. Med. Genet. 38:411‐417.
   Kitsberg, D., Selig, S., Brandeis, M., Simon, I., Keshet, I., Driscoll, D.J., Nicholls, R.D., and Cedar, H. 1993. Allele‐specific replication timing of imprinted gene regions. Nature 364:459‐463.
   Knight, S.J., Horsley, S.W., Regan, R., Lawrie, N.M., Maher, E.J., Cardy, D.L., Flint, J., and Kearney, L. 1997. Development and clinical application of an innovative fluorescence in situ hybridization technique which detects submicroscopic rearrangements involving telomeres. Eur. J. Hum. Genet. 5:1‐8.
   Krantz, I.D., Colliton, R.P., Genin, A., Rand, E.B., Li, L., Piccoli, D.A., and Spinner, N.B. 1998. Spectrum and frequency of jagged1 (JAG1) mutations in Alagille syndrome patients and their families. Am. J. Hum. Genet. 62:1361‐1369.
   Kurotaki, N., Harada, N., Shimokawa, O., Miyake, N., Kawame, H., Uetake, K., Makita, Y., Kondoh, T., Ogata, T., Hasegawa, T., Nagai, T., Ozaki, T., Touyama, M., Shenhav, R., Ohashi, H., Medne, L., Shiihara, T., Ohtsu, S., Kato, Z., Okamoto, N., Nishimoto, J., Lev, D., Miyoshi, Y., Ishikiriyama, S., Sonoda, T., Sakazume, S., Fukushima, Y., Kurosawa, K., Cheng, J.F., Yoshiura, K., Ohta, T., Kishino, T., Niikawa, N., and Matsumoto, N. 2003. Fifty microdeletions among 112 cases of Sotos syndrome: Low copy repeats possibly mediate the common deletion. Hum. Mutat. 22:378‐387.
   Kuwano, A., Ledbetter, S.A., Dobyns, W.B., Emanuel, B.S., and Ledbetter, D.H. 1991. Detection of deletions and cryptic translocations in Miller‐Dieker syndrome by in situ hybridization. Am. J. Hum. Genet. 49:707‐714.
   Kuwano, A., Mutirangura, A., Dittrich, B., Buiting, K., Horsthemke, B., Saitoh, S., Niikawa, N., Ledbetter, S.A., Greenberg, F., Chinault, A.C., and Ledbetter, D.H. 1992. Molecular dissection of the Prader‐Willi/Angelman syndrome region (15q11‐13) by YAC cloning and FISH analysis. Hum. Mol. Genet. 1:417‐425.
   Ledbetter, D.H., Riccardi, V.M., Airhart, S.D., Strobel, R.J., Keenan, B.S., and Crawford, J.D. 1981. Deletions of chromosome 15 as a cause of the Prader‐Willi syndrome. N. Engl. J. Med. 304:325‐329.
   Ledbetter, S.A., Kuwano, A., Dobyns, W.B., and Ledbetter, D.H. 1992. Microdeletions of chromosome 17p13 as a cause of isolated lissencephaly. Am. J. Hum. Genet. 50:182‐189.
   Le Guern, E., Sturtz, F., Gugenheim, M., Gouider, R., Bonnebouche, C., Ravise, N., Gonnaud, P.M., Tardieu, S., Bouche, P., Chazot, G., et al. 1994. Detection of deletion within 17p11.2 in 7 French families with hereditary neuropathy with liability to pressure palsies (HNPP). Cytogenet. Cell Genet. 65:261‐264.
   Lejeune, L., Lafourcade, J., de Grouchy, J., Berger, R., Gautier, M., Salmon, C., and Turpin, R. 1963. Deletion partielle du bras court du chromosome 5. Individualisation d'un nouvel etat morbide. Sem. Hop. Paris 18:1069‐1079.
   Lenssen, P.P., Gabreels‐Festen, A.A., Valentijn, L.J., Jongen, P.J., van Beersum, S.E., van Engelen, B.G., van Wensen, P.J., Bolhuis, P.A., Gabreels, F.J., and Mariman, E.C. 1998. Hereditary neuropathy with liability to pressure palsies. Phenotypic differences between patients with the common deletion and a PMP22 frame shift mutation. Brain 121:1451‐1458.
   Li, M., Squire, J.A., and Weksberg, R. 1998. Molecular genetics of Wiedemann‐Beckwith syndrome. Am. J. Med. Genet. 79:253‐259.
   Lichter, P., Boyle, A.L., Cremer, T., and Ward, D.C. 1991. Analysis of genes and chromosomes by nonisotopic in situ hybridization. Genet. Anal. Tech. Appl. 8:24‐35.
   Lindlof, M., Kaariainen, H., van Ommen, G.J., and de la Chapelle, A. 1988. Microdeletions in patients with X‐linked muscular dystrophy: Molecular‐clinical correlations. Clin. Genet. 33:131‐139.
   Lopes, J., Tardieu, S., Silander, K., Blair, I., Vandenberghe, A., Palau, F., Ruberg, M., Brice, A., and LeGuern, E. 1999. Homologous DNA exchanges in humans can be explained by the yeast double‐strand break repair model: A study of 17p11.2 rearrangements associated with CMT1A and HNPP. Hum. Mol. Genet. 8:2285‐2292.
   Lowery, M.C., Morris, C.A., Ewart, A., Brothman, L.J., Zhu, X.L., Leonard, C.O., Carey, J.C., Keating, M., and Brothman, A.R. 1995. Strong correlation of elastin deletions, detected by FISH, with Williams syndrome: Evaluation of 235 patients. Am. J. Hum. Genet. 57:49‐53.
   Luciani, J.J., de Mas, P., Depetris, D., Mignon‐Ravix, C., Bottani, A., Prieur, M., Jonveaux, P., Philippe, A., Bourrouillou, G., de Martinville, B., Delobel, B., Vallee, L., Croquette, M.F., and Mattei, M.G. 2003. Telomeric 22q13 deletions resulting from rings, simple deletions, and translocations: Cytogenetic, molecular, and clinical analyses of 32 new observations. J. Med. Genet. 40:690‐696.
   Ludecke, H.J., Wagner, M.J., Nardmann, J., La Pillo, B., Parrish, J.E., Willems, P.J., Haan, E.A., Frydman, M., Hamers, G.J., Wells, D.E., et al. 1995. Molecular dissection of a contiguous gene syndrome: localization of the genes involved in the Langer‐Giedion syndrome. Hum. Mol. Genet. 4:31‐36.
   Ludecke, H.J., Schaper, J., Meinecke, P., Momeni, P., Gross, S., von Holtum, D., Hirche, H., Abramowicz, M.J., Albrecht, B., Apacik, C., Christen, H.J., Claussen, U., Devriendt, K., Fastnacht, E., Forderer, A., Friedrich, U., Goodship, T.H., Greiwe, M., Hamm, H., Hennekam, R.C., Hinkel, G.K., Hoeltzenbein, M., Kayserili, H., Majewski, F., Mathieu, M., McLeod, R., Midro, A.T., Moog, U., Nagai, T., Niikawa, N., Orstavik, K.H., Plochl, E., Seitz, C., Schmidtke, J., Tranebjaerg, L., Tsukahara, M., Wittwer, B., Zabel, B., Gillessen‐Kaesbach, G., and Horsthemke, B. 2001. Genotypic and phenotypic spectrum in tricho‐rhino‐phalangeal syndrome types I and III. Am. J. Hum. Genet. 68:81‐91.
   Lupski, J.R. 1998. Genomic disorders: Structural features of the genome can lead to DNA rearrangements and human disease traits. Trends Genet. 14:417‐422.
   Lupski, J.R., de Oca‐Luna, R.M., Slaugenhaupt, S., Pentao, L., Guzzetta, V., Trask, B.J., Saucedo‐Cardenas, O., Barker, D.F., Killian, J.M., Garcia, C.A., Chakravarti, A., and Patel, P.I. 1991. DNA duplication associated with Charcot‐Marie‐Tooth disease type 1A. Cell 66:219‐232.
   Magenis, R.E., Brown, M.G., Lacy, D.A., Budden, S., and LaFranchi, S. 1987. Is Angelman syndrome an alternate result of del(15)(q11q13)? Am. J. Med. Genet. 28:829‐838.
   Magenis, R.E., Toth‐Fejel, S., Allen, L.J., Black, M., Brown, M.G., Budden, S., Cohen, R., Friedman, J.M., Kalousek, D., Zonana, J., et al. 1990. Comparison of the 15q deletions in Prader‐Willi and Angelman syndromes: Specific regions, extent of deletions, parental origin, and clinical consequences. Am. J. Med. Genet. 35:333‐349.
   Mainardi, P.C., Perfumo, C., Cali, A., Coucourde, G., Pastore, G., Cavani, S., Zara, F., Overhauser, J., Pierluigi, M., and Bricarelli, F.D. 2001. Clinical and molecular characterisation of 80 patients with 5p deletion: Genotype‐phenotype correlation. J. Med. Genet. 38:151‐158.
   Mantripragada, K.K., Tapia‐Paez, I., Blennow, E., Nilsson, P., Wedell, A., and Dumanski, J.P. 2004. DNA copy‐number analysis of the 22q11 deletion‐syndrome region using array‐CGH with genomic and PCR‐based targets. Int. J. Mol. Med. 13:273‐279.
   McElreavey, K. and Cortes, L.S. 2001. X‐Y translocations and sex differentiation. Semin. Reprod. Med. 19:133‐139.
   McElreavy, K., Vilain, E., Abbas, N., Costa, J.M., Souleyreau, N., Kucheria, K., Boucekkine, C., Thibaud, E., Brauner, R., Flamant, F., et al. 1992. XY sex reversal associated with a deletion 5′ to the SRY “HMG box” in the testis‐determining region. Proc. Natl. Acad. Sci. U.S.A. 89:11016‐11020.
   Miller, D.T., Shen, Y., Weiss, L.A., Korn, J., Anselm, I., Bridgemohan, C., Cox, G.F., Dickinson, H., Gentile, J., Harris, D.J., Hegde, V., Hundley, R., Khwaja, O., Kothare, S., Luedke, C., Nasir, R., Poduri, A., Prasad, K., Raffalli, P., Reinhard, A., Smith, S.E., Sobeih, M.M., Soul, J.S., Stoler, J., Takeoka, M., Tan, W.H., Thakuria, J., Wolff, R., Yusupov, R., Gusella, J.F., Daly, M.J., and Wu, B.L. 2009. Microdeletion/duplication at 15q13.2q13.3 among individuals with features of autism and other neuropsychiatric disorders. J. Med. Genet. 46:242‐248.
   Momeni, P., Glockner, G., Schmidt, O., von Holtum, D., Albrecht, B., Gillessen‐Kaesbach, G., Hennekam, R., Meinecke, P., Zabel, B., Rosenthal, A., Horsthemke, B., and Ludecke, H.J. 2000. Mutations in a new gene, encoding a zinc‐finger protein, cause tricho‐rhino‐phalangeal syndrome type I. Nat. Genet. 24:71‐74.
   Muller, U. 1987. Mapping of testis‐determining locus on Yp by the molecular genetic analysis of XX males and XY females. Development 101:51‐58.
   Nardmann, J., Tranebjaerg, L., Horsthemke, B., Ludecke, H.J. 1997. The tricho‐rhino‐phalangeal syndromes: Frequency and parental origin of 8q deletions. Hum. Genet. 99:638‐643.
   Nickerson, E., Greenberg, F., Keating, M.T., McCaskill, C., and Shaffer, L.G. 1995. Deletions of the elastin gene at 7q11.23 occur in approximately 90% of patients with Williams syndrome. Am. J. Hum. Genet. 56:1156‐1161.
   Ning, Y., Rosenberg, M., Biesecker, L.G., and Ledbetter, D.H. 1996. Isolation of the human chromosome 22q telomere and its application to detection of cryptic chromosomal abnormalities. Hum. Genet. 97:765‐769.
   Okamoto, N., Kubota, T., Nakamura, Y., Murakami, R., Nishikubo, T., Tanaka, I., Takahashi, Y., Hayashi, S., Imoto, I., Inazawa, J., Hosokai, N., Kohsaka, S., and Uchino, S. 2007. 22q13 Microduplication in two patients with common clinical manifestations: A recognizable syndrome? Am. J. Med. Genet. A 143A:2804‐2809.
   Penrose, L.S., Ellis, J.R., and Delhanty, J.D. 1960. Chromosomal translocations in mongolism and in normal relatives. Lancet 2:409‐410.
   Peter, M., Viemann, M., Partsch, C.J., and Sippell, W.G. 1998. Congenital adrenal hypoplasia: Clinical spectrum, experience with hormonal diagnosis, and report on new point mutations of the DAX‐1 gene. J. Clin. Endocrinol. Metab. 83:2666‐2674.
   Petrij, F., Dauwerse, H.G., Blough, R.I., Giles, R.H., van der Smagt, J.J., Wallerstein, R., Maaswinkel‐Mooy, P.D., van Karnebeek, C.D., van Ommen, G.J., van Haeringen, A., Rubinstein, J.H., Saal, H.M., Hennekam, R.C., Peters, D.J., and Breuning, M.H. 2000. Diagnostic analysis of the Rubinstein‐Taybi syndrome: Five cosmids should be used for microdeletion detection and low number of protein truncating mutations. J. Med. Genet. 37:168‐176.
   Phelan, M.C., Rogers, R.C., Saul, R.A., Stapleton, G.A., Sweet, K., McDermid, H., Shaw, S.R., Claytor, J., Willis, J., and Kelly, D.P. 2001. 22q13 deletion syndrome. Am. J. Med. Genet. 101:91‐99.
   Polani, P.E., Briggs, J.H., Ford, C.E., Clarke, C.M., and Berg, J.M. 1960. A Mongol girl with 46 chromosomes. Lancet 1:721‐724.
   Potocki, L. and Shaffer, L.G. 1996. Interstitial deletion of 11(p11.2p12): A newly described contiguous gene deletion syndrome involving the gene for hereditary multiple exostoses (EXT2). Am. J. Med. Genet. 62:319‐325.
   Potocki, L., Chen, K.S., Park, S.S., Osterholm, D.E., Withers, M.A., Kimonis, V., Summers, A.M., Meschino, W.S., Anyane‐Yeboa, K., Kashork, C.D., Shaffer, L.G., and Lupski, J.R. 2000. Molecular mechanism for duplication 17p11.2‐ the homologous recombination reciprocal of the Smith‐Magenis microdeletion. Nat. Genet. 24:84‐87.
   Potocki, L., Bi, W., Treadwell‐Deering, D., Carvalho, C.M., Eifert, A., Friedman, E.M., Glaze, D., Krull, K., Lee, J.A., Lewis, R.A., Mendoza‐Londono, R., Robbins‐Furman, P., Shaw, C., Shi, X., Weissenberger, G., Withers, M., Yatsenko, S.A., Zackai, E.H., Stankiewicz, P., and Lupski, J.R. 2007. Characterization of Potocki‐Lupski syndrome (dup(17)(p11.2p11.2)) and delineation of a dosage‐sensitive critical interval that can convey an autism phenotype. Am. J. Hum. Genet. 80:633‐649.
   Prakash, S.K., Cormier, T.A., McCall, A.E., Garcia, J.J., Sierra, R., Haupt, B., Zoghbi, H.Y., and Van Den Veyver, I.B. 2002. Loss of holocytochrome c‐type synthetase causes the male lethality of X‐linked dominant microphthalmia with linear skin defects (MLS) syndrome. Hum. Mol. Genet. 11:3237‐3248.
   Rauch, A., Zink, S., Zweier, C., Thiel, C.T., Koch, A., Rauch, R., Lascorz, J., Huffmeier, U., Weyand, M., Singer, H., and Hofbeck, M. 2005. Systematic assessment of atypical deletions reveals genotype‐phenotype correlation in 22q11.2. J. Med. Genet. 42:871‐876.
   Ravnan, J.B., Tepperberg, J.H., Papenhausen, P., Lamb, A.N., Hedrick, J., Eash, D., Ledbetter, D.H., and Martin, C.L. 2006. Subtelomere FISH analysis of 11 688 cases: An evaluation of the frequency and pattern of subtelomere rearrangements in individuals with developmental disabilities. J. Med. Genet. 43:478‐489.
   Richter, S., Vandezande, K., Chen, N., Zhang, K., Sutherland, J., Anderson, J., Han, L., Panton, R., Branco, P., and Gallie, B. 2003. Sensitive and efficient detection of RB1 gene mutations enhances care for families with retinoblastoma. Am. J. Hum. Genet. 72:253‐269.
   Ried, T., Mahler, V., Vogt, P., Blonden, L., van Ommen, G.J., Cremer, T., and Cremer, M. 1990. Direct carrier detection by in situ suppression hybridization with cosmid clones of the Duchenne/Becker muscular dystrophy locus. Hum. Genet. 85:581‐586.
   Rosias, P.R., Sijstermans, J.M., Theunissen, P.M., Pulles‐Heintzberger, C.F., De Die‐Smulders, C.E., Engelen, J.J., and Van Der Meer, S.B. 2001. Phenotypic variability of the cat eye syndrome. Case report and review of the literature. Genet. Couns. 12:273‐282.
   Royer‐Pokora, B., Beier, M., Henzler, M., Alam, R., Schumacher, V., Weirich, A., and Huff, V. 2004. Twenty‐four new cases of WT1 germline mutations and review of the literature: Genotype/phenotype correlations for Wilms tumor development. Am. J. Med. Genet. A 127A:249‐257.
   Sargent, C.A., Kidd, A., Moore, S., Dean, J., Besley, G.T., and Affara, N.A. 2000. Five cases of isolated glycerol kinase deficiency, including two families: Failure to find genotype:phenotype correlation. J. Med. Genet. 37:434‐441.
   Sato, N., Katsumata, N., Kagami, M., Hasegawa, T., Hori, N., Kawakita, S., Minowada, S., Shimotsuka, A., Shishiba, Y., Yokozawa, M., Yasuda, T., Nagasaki, K., Hasegawa, D., Hasegawa, Y., Tachibana, K., Naiki, Y., Horikawa, R., Tanaka, T., and Ogata, T. 2004. Clinical assessment and mutation analysis of Kallmann syndrome 1 (KAL1) and fibroblast growth factor receptor 1 (FGFR1, or KAL2) in five families and 18 sporadic patients. J. Clin. Endocrinol. Metab. 89:1079‐1088.
   Scherer, G., Held, M., Erdel, M., Meschede, D., Horst, J., Lesniewicz, R., and Midro, A.T. 1998. Three novel SRY mutations in XY gonadal dysgenesis and the enigma of XY gonadal dysgenesis cases without SRY mutations. Cytogenet. Cell Genet. 80:188‐192.
   Seranski, P., Heiss, N.S., Dhorne‐Pollet, S., Radelof, U., Korn, B., Hennig, S., Backes, E., Schmidt, S., Wiemann, S., Schwarz, C.E., Lehrach, H., and Poustka, A. 1999. Transcription mapping in a medulloblastoma breakpoint interval and Smith‐Magenis syndrome candidate region: Identification of 53 transcriptional units and new candidate genes. Genomics 56:1‐11.
   Shaffer, L.G., Kennedy, G.M., Spikes, A.S., and Lupski, J.R. 1997. Diagnosis of CMT1A duplications and HNPP deletions by interphase FISH: Implications for testing in the cytogenetics laboratory. Am. J. Med. Genet. 69:325‐331.
   Shaffer, L.G., Ledbetter, D.H., and Lupski, J.R. 2001. Molecular cytogenetics of contiguous gene syndromes: Mechanisms and consequences of gene dosage imbalance. In: Metabolic and Molecular Basis of Inherited Disease 8th ed. (C.R. Scriver, A.L. Beaudet, W.S. Sly, D. Valle, B. Childs, K.W. Kinzler, and B. Vogelstein, eds.) pp. 1291‐1324. McGraw Hill, New York.
   Shaikh, T.H., Kurahashi, H., Saitta, S.C., O'Hare, A.M., Hu, P., Roe, B.A., Driscoll, D.A., McDonald‐McGinn, D.M., Zackai, E.H., Budarf, M.L., and Emanuel, B.S. 2000. Chromosome 22‐specific low copy repeats and the 22q11.2 deletion syndrome: Genomic organization and deletion endpoint analysis. Hum. Mol. Genet. 9:489‐501.
   Shapiro, L.J., Yen, P., Pomerantz, D., Martin, E., Rolewic, L., and Mohandas, T. 1989. Molecular studies of deletions at the human steroid sulfatase locus. Proc. Natl. Acad. Sci. U.S.A. 86:8477‐8481.
   Sharp, A.J., Mefford, H.C., Li, K., Baker, C., Skinner, C., Stevenson, R.E., Schroer, R.J., Novara, F., De Gregori, M., Ciccone, R., Broomer, A., Casuga, I., Wang, Y., Xiao, C., Barbacioru, C., Gimelli, G., Bernardina, B.D., Torniero, C., Giorda, R., Regan, R., Murday, V., Mansour, S., Fichera, M., Castiglia, L., Failla, P., Ventura, M., Jiang, Z., Cooper, G.M., Knight, S.J., Romano, C., Zuffardi, O., Chen, C., Schwartz, C.E., and Eichler, E.E. 2008. A recurrent 15q13.3 microdeletion syndrome associated with mental retardation and seizures. Nat. Genet. 40:322‐328.
   Shevell, M., Ashwal, S., Donley, D., Flint, J., Gingold, M., Hirtz, D., Majnemer, A., Noetzel, M., and Sheth, R.D. 2003. Practice parameter: Evaluation of the child 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 60:367‐380.
   Slager, R.E., Newton, T.L., Vlangos, C.N., Finucane, B., and Elsea, S.H. 2003. Mutations in RAI1 associated with Smith‐Magenis syndrome. Nat. Genet. 33:466‐468.
   Slavotinek, A.M. 2008. Novel microdeletion syndromes detected by chromosome microarrays. Hum. Genet. 124:1‐17.
   Slavotinek, A.M., Gaunt, L., and Donnai, D. 1997. Paternally inherited duplications of 11p15.5 and Beckwith‐Wiedemann syndrome. J. Med. Genet. 34:819‐826.
   Smith, A.C., McGavran, L., Robinson, J., Waldstein, G., Macfarlane, J., Zonona, J., Reiss, J., Lahr, M., Allen, L., and Magenis, E. 1986. Interstitial deletion of (17)(p11.2p11.2) in nine patients. Am. J. Med. Genet. 24:393‐414.
   Somerville, M.J., Mervis, C.B., Young, E.J., Seo, E.J., del Campo, M., Bamforth, S., Peregrine, E., Loo, W., Lilley, M., Perez‐Jurado, L.A, Morris, C.A., Scherer, S.W., and Osborne, L.R. 2005. Severe expressive‐language delay related to duplication of the Williams‐Beuren locus. N. Engl. J. Med. 353:1694‐1701.
   Spinner, N.B., Colliton, R.P., Crosnier, C., Krantz, I.D., Hadchouel, M., and Meunier‐Rotival, M. 2001. Jagged1 mutations in alagille syndrome. Hum. Mutat. 17:18‐33.
   Srour, M., Bejjani, B.A., Rorem, E.A., Hall, N., Shaffer, L.G., and Shevell, M.I. 2008. An instructive case of an 8‐year‐old boy with intellectual disability. Semin. Pediatr. Neurol. 15:154‐155.
   Stratton, R.F., Dobyns, W.B., Airhart, S.D., and Ledbetter, D.H. 1984. New chromosomal syndrome: Miller‐Dieker syndrome and monosomy 17p13. Hum. Genet. 67:193‐200.
   Taine, L., Goizet, C., Wen, Z.Q., Petrij, F., Breuning, M.H., Ayme, S., Saura, R., Arveiler, B., and Lacombe, D. 1998. Submicroscopic deletion of chromosome 16p13.3 in patients with Rubinstein‐Taybi syndrome. Am. J. Med. Genet. 78:267‐270.
   Tatton‐Brown, K., Douglas, J., Coleman, K., Baujat, G., Chandler, K., Clarke, A., Collins, A., Davies, S., Faravelli, F., Firth, H., Garrett, C., Hughes, H., Kerr, B., Liebelt, J., Reardon, W., Schaefer, G.B., Splitt, M., Temple, I.K., Waggoner, D., Weaver, D.D., Wilson, L., Cole, T., Cormier‐Daire, V., Irrthum, A., and Rahman, N. 2005. Multiple mechanisms are implicated in the generation of 5q35 microdeletions in Sotos syndrome. J. Med. Genet. 42:307‐313.
   Tocharoentanaphol, C., Cremer, M., Schrock, E., Blonden, L., Kilian, K., Cremer, T., and Ried, T. 1994. Multicolor fluorescence in situ hybridization on metaphase chromosomes and interphase Halo‐preparations using cosmid and YAC clones for the simultaneous high resolution mapping of deletions in the dystrophin gene. Hum. Genet. 93:229‐235.
   Torres‐Juan, L., Rosell, J., Morla, M., Vidal‐Pou, C., Garcia‐Algas, F., de la Fuente, M.A., Juan, M., Tubau, A., Bachiller, D., Bernues, M., Perez‐Granero, A., Govea, N., Busquets, X., and Heine‐Suner, D. 2007. Mutations in TBX1 genocopy the 22q11.2 deletion and duplication syndromes: A new susceptibility factor for mental retardation. Eur. J. Hum. Genet. 15:658‐663.
   Trask, BJ. 1991. Fluorescence in situ hybridization: Applications in cytogenetics and gene mapping. Trends Genet. 7:149‐154.
   Turkmen, S., Gillessen‐Kaesbach, G., Meinecke, P., Albrecht, B., Neumann, L.M., Hesse, V., Palanduz, S., Balg, S., Majewski, F., Fuchs, S., Zschieschang, P., Greiwe, M., Mennicke, K., Kreuz, F.R., Dehmel, H.J., Rodeck, B., Kunze, J., Tinschert, S., Mundlos, S., and Horn, D. 2003. Mutations in NSD1 are responsible for Sotos syndrome, but are not a frequent finding in other overgrowth phenotypes. Eur. J. Hum. Genet. 11:858‐865.
   Upadhyaya, M., Ruggieri, M., Maynard, J., Osborn, M., Hartog, C., Mudd, S., Penttinen, M., Cordeiro, I., Ponder, M., Ponder, B.A., Krawczak, M., and Cooper, D.N. 1998. Gross deletions of the neurofibromatosis type 1 (NF1) gene are predominantly of maternal origin and commonly associated with a learning disability, dysmorphic features and developmental delay. Hum. Genet. 102:591‐597.
   Van Buggenhout, G., Melotte, C., Dutta, B., Froyen, G., Van Hummelen, P., Marynen, P., Matthijs, G., de Ravel, T., Devriendt, K., Fryns, J.P., and Vermeesch, J.R. 2004. Mild Wolf‐Hirschhorn syndrome: Micro‐array CGH analysis of atypical 4p16.3 deletions enables refinement of the genotype‐phenotype map. J. Med. Genet. 41:691‐698.
   Van Esch, H., Groenen, P., Daw, S., Poffyn, A., Holvoet, M., Scambler, P., Fryns, J.P., Van de Ven, W., and Devriendt, K. 1999. Partial DiGeorge syndrome in two patients with a 10p rearrangement. Clin. Genet. 55:269‐276.
   Vissers, L.E., van Ravenswaaij, C.M., Admiraal, R., Hurst, J.A., de Vries, B.B., Janssen, I.M., van der Vliet, W.A., Huys, E.H., de Jong, P.J., Hamel, B.C., Schoenmakers, E.F., Brunner, H.G., Veltman, J.A., and van Kessel, A.G. 2004. Mutations in a new member of the chromodomain gene family cause CHARGE syndrome. Nat. Genet. 36:955‐957.
   Vlangos, C.N., Yim, D.K., and Elsea, SH. 2003. Refinement of the Smith‐Magenis syndrome critical region to approximately 950kb and assessment of 17p11.2 deletions. Are all deletions created equally? Mol. Genet. Metab. 79:134‐141.
   Voskova‐Goldman, A., Peier, A., Caskey, C.T., Richards, C.S., and Shaffer, L.G. 1997. DMD‐specific FISH probes are diagnostically useful in the detection of female carriers of DMD gene deletions. Neurology 48:1633‐1638.
   Waggoner, D.J., Raca, G., Welch, K., Dempsey, M., Anderes, E., Ostrovnaya, I., Alkhateeb, A., Kamimura, J., Matsumoto, N., Schaeffer, G.B., Martin, C.L., and Das, S. 2005. NSD1 analysis for Sotos syndrome: Insights and perspectives from the clinical laboratory. Genet. Med. 7:524‐533.
   Wakui, K., Gregato, G., Ballif, B.C., Glotzbach, C.D., Bailey, K.A., Kuo, P.L., Sue, W.C., Sheffield, L.J., Irons, M., Gomez, E.G., Hecht, J.T., Potocki, L., and Shaffer, L.G. 2005. Construction of a natural panel of 11p11.2 deletions and further delineation of the critical region involved in Potocki‐Shaffer syndrome. Eur. J. Hum. Genet. 13:528‐540.
   Wang, N.J., Liu, D., Parokonny, A.S., and Schanen, NC. 2004. High‐resolution molecular characterization of 15q11‐q13 rearrangements by array comparative genomic hybridization (array CGH) with detection of gene dosage. Am. J. Hum. Genet. 75:267‐281.
   Ware, S.M., Peng, J., Zhu, L., Fernbach, S., Colicos, S., Casey, B., Towbin, J., and Belmont, J.W. 2004. Identification and functional analysis of ZIC3 mutations in heterotaxy and related congenital heart defects. Am. J. Hum. Genet. 74:93‐105.
   Wentzel, C., Fernstrom, M., Ohrner, Y., Anneren, G., and Thuresson, A.C. 2008. Clinical variability of the 22q11.2 duplication syndrome. Eur. J. Med. Genet. 51:501‐510.
   Willatt, L., Cox, J., Barber, J., Cabanas, E.D., Collins, A., Donnai, D., FitzPatrick, D.R., Maher, E., Martin, H., Parnau, J., Pindar, L., Ramsay, J., Shaw‐Smith, C., Sistermans, E.A., Tettenborn, M., Trump, D., de Vries, B.B., Walker, K., and Raymond, F.L. 2005. 3q29 microdeletion syndrome: Clinical and molecular characterization of a new syndrome. Am. J. Hum. Genet. 77:154‐160.
   Wolf, U., Reinwein, H., Porsch, R., Schroter, R., and Baitsch, H. 1965. Defizienz an den kurzen Armen eines chromosomes n 4. Humangenetik 1:397‐413.
   Woodward, K., Kendall, E., Vetrie, D., and Malcolm, S. 1998. Pelizaeus‐Merzbacher disease: Identification of Xq22 proteolipid‐protein duplications and characterization of breakpoints by interphase FISH. Am. J. Hum. Genet. 63:207‐217.
   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., and Matsuoka, R. 2003. Role of TBX1 in human del22q11.2 syndrome. Lancet 362:1366‐1373.
   Yobb, T.M., Somerville, M.J., Willatt, L., Firth, H.V., Harrison, K., MacKenzie, J., Gallo, N., Morrow, B.E., Shaffer, L.G., Babcock, M., Chernos, J., Bernier, F., Sprysak, K., Christiansen, J., Haase, S., Elyas, B., Lilley, M., Bamforth, S., and McDermid, H.E. 2005. Microduplication and triplication of 22q11.2: A highly variable syndrome. Am. J. Hum. Genet. 76:865‐876.
   Yu, W., Ballif, B.C., Kashork, C.D., Heilstedt, H.A., Howard, L.A., Cai, W.W., White, L.D., Liu, W., Beaudet, A.L., Bejjani, B.A., Shaw, C.A., and Shaffer, L.G. 2003. Development of a comparative genomic hybridization microarray and demonstration of its utility with 25 well‐characterized 1p36 deletions. Hum. Mol. Genet. 12:2145‐2152.
   Yunis, J.J. 1976. High resolution of human chromosomes. Science 191:1268‐1270.
   Zackowski, J.L., Nicholls, R.D., Gray, B.A., Bent‐Williams, A., Gottlieb, W., Harris, P.J., Waters, M.F., Driscoll, D.J., Zori, R.T., and Williams, C.A. 1993. Cytogenetic and molecular analysis in Angelman syndrome. Am. J. Med. Genet. 46:7‐11.
   Zhang, X., Snijders, A., Segraves, R., Zhang, X., Niebuhr, A., Albertson, D., Gray, J., Yang, H., Niebuhr, E., Bolund, L., and Pinkel, D. 2005. High‐resolution mapping of genotype‐phenotype relationships in cri du chat syndrome using array comparative genomic hybridization. Am. J. Hum. Genet. 76:312‐326.
   Zori, R.T., Lupski, J.R., Heju, Z., Greenberg, F., Killian, J.M., Gray, B.A., Driscoll, D.J., Patel, P.I., and Zackowski, J.L. 1993. Clinical, cytogenetic, and molecular evidence for an infant with Smith‐Magenis syndrome born from a mother having a mosaic 17p11.2p12 deletion. Am. J. Med. Genet. 47:504‐511.
   Zvulunov, A., Kachko, L., Manor, E., Shinwell, E., and Carmi, R. 1998. Reticulolinear aplasia cutis congenita of the face and neck: A distinctive cutaneous manifestation in several syndromes linked to Xp22. Br. J. Dermatol. 138:1046‐1052.
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