Skip to main content Accessibility help

We use cookies to distinguish you from other users and to provide you with a better experience on our websites. Close this message to accept cookies or find out how to manage your cookie settings.

Close cookie message
×
Hostname: page-component-cd9895bd7-q99xh Total loading time: 0 Render date: 2024-12-27T12:49:05.084Z Has data issue: false hasContentIssue false

2 - Molecular genetics of velo-cardio-facial syndrome

Published online by Cambridge University Press:  11 August 2009

By
Katrina Prescott  and
Peter J. Scambler
Edited by
Kieran C. Murphy  and
Peter J. Scambler
Peter J. Scambler
Affiliation:
Molecular Medicine Unit, Institute of Child Health, London, UK
Kieran C. Murphy
Affiliation:
Education and Research Centre, Royal College of Surgeons of Ireland
Peter J. Scambler
Affiliation:
Institute of Child Health, University College London
Get access

Summary

Introduction

It has been known for over a decade that the majority of cases of DiGeorge Syndrome (DGS) and velo-cardio-facial syndrome (VCFS) are caused by an interstitial deletion of chromosome 22q11 (Carey et al., 1992). Rarely, terminal deletions and balanced translocations involving chromosome 22q11 may also cause the syndrome, and some cases appear to have a robust diagnosis but no deletion. Estimates of the frequency with which the deletions occur have been made from populations where ascertainment is thought to be particularly high and generally suggest an incidence of 1: 4000 live births (Wilson et al., 1994; Du Montcel et al., 1996); 5–10% of deletions are inherited (Ryan et al., 1997). Molecular studies have shown that most patients have a 3Mb interstitial deletion – the typically deleted region, or TDR – a minority having somewhat smaller (1.5–2 Mb) deletions (Emanuel et al., 1998). As will be evident from other chapters in this volume there is a great deal of variation in severity and type of malformation between patients. However, there is no evidence that the size or the precise endpoints of the deletion have any influence on phenotype. Variation of phenotype extends to individuals within the same family and, as molecular studies have shown that deletion size is stable in different members of the same family, this cannot be ascribed to subtle differences in the extent or position of the deletion. Moreover, phenotypic discordance between monozygotic twins has been described (Goodship et al., 1995).

Keywords

22q11 deletion syndromebehavioral difficultyinterstitial chromosome deletionmolecular geneticsprenatal diagnosisvelo-cardio-facial syndrome
Type
Chapter
Information
Velo-Cardio-Facial Syndrome
A Model for Understanding Microdeletion Disorders
 , pp. 19 - 46
Publisher: Cambridge University Press
Print publication year: 2005

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Abu-Issa, R., Smyth, G., Smoak, I.et al. (2002) Fgf8 is required for pharyngeal arch and cardiovascular development in the mouse. Development, 129 (19), 4613–25.Google Scholar
Akhavan, S., Cristofaro, R., Peyvandi, F.et al. (2002) Molecular and functional characterization of a natural homozygous Arg67His mutation in the prothrombin gene of a patient with a severe procoagulant defect contrasting with a mild hemorrhagic phenotype, Blood, 100 (4), 1347–53.Google Scholar
Amati, F., Conti, E., Novelli, A.et al. (1999) Atypical deletions suggest five 22q11.2 critical regions related to the DiGeorge/velo-cardio-facial syndrome, Eur. J. Hum. Genet., 7 (8), 903–9.Google Scholar
Augusseau, S., Jouk, S., Jalbert, P. & Priur, M. (1986) DiGeorge syndrome and 22q11 rearrangements, Hum. Genet., 74, 206.Google Scholar
Ayuk, P. T., Sibley, C. P., Donnai, P.et al. (2000) Development and polarization of cationic amino acid transporters and regulators in the human placenta, Am. J. Physiol. Cell Physiol., 278 (6), C1162–71.Google Scholar
Bachiller, D., Klingensmith, J., Shneyder, N.et al. (2003) The role of chordin/Bmp signals in mammalian pharyngeal development and DiGeorge syndrome. Development, 130 (15), 3567–78.Google Scholar
Baglin, T. P., Carrell, R. W., Church, F. C.et al. (2002) Crystal structures of native and thrombin-complexed heparin cofactor II reveal a multistep allosteric mechanism. Proc. Natl. Acad. Sci. USA, 99 (17), 11079–84.Google Scholar
Baldini, A. (2000) DiGeorge syndrome: complex pathogenesis? Maybe, maybe not. Mol. Med. Today, 6 (1), 12.Google Scholar
Berend, S. A., Spikes, A. S., Kashork, C. D.et al. (2000) Dual-probe fluorescence in situ hybridization assay for detecting deletions associated with VCFS/DiGeorge syndrome I and DiGeorge syndrome II loci [In Process Citation]. Am. J. Med. Genet., 91 (4), 313–17.Google Scholar
Bergman, A. & Blennow, E. (2000) Inv dup (22), del (22) (q11) and r (22) in the father of a child with DiGeorge syndrome. Eur. J. Hum. Genet., 8 (10), 801–4.Google Scholar
Berti, L., Mittler, G., Przemeck, G. K.et al. (2001) Isolation and characterization of a novel gene from the DiGeorge chromosomal region that encodes for a mediator subunit. Genomics, 74 (3), 320–32.Google Scholar
Binder, M. (1985) The teratogenic effects of a Bis (dichloroacetyl)diamine on hamster embryos. Am. J. Pathol., 118, 179–93.Google Scholar
Bobanovic, L. K., Royle, S. J. & Murrell-Lagnado, R. D. (2002) P2X receptor trafficking in neurons is subunit specific. J. Neurosci., 22 (12), 4814–24.Google Scholar
Bockman, D. E. & Kirby, M. L. (1984) Dependence of thymus development on derivatives of the neural crest. Science, 223, 498–500.Google Scholar
Bockman, D. E., Redmond, M. E., Waldo, K.et al. (1987) Effect of neural crest ablation on development of the heart and arch arteries in the chick. Am. J. Anat., 180, 332–41.Google Scholar
Botta, A., Lindsay, E. A., Jurecic, V. & Baldini, A. (1997) Comparative mapping of the DiGeorge syndrome region in mouse shows inconsistent gene order and diferential degree of gene conservation. Mammalian Genome, 8, 890–5.Google Scholar
Budarf, M. L., Konkle, B. A., Ludlow, L. B.et al. (1995) Identification of a patient with Bernard–Soulier syndrome and a deletion in the DiGeorge/Velo-cardio-facial chromosomal region in 22q11.2., Hum Mol Genet, 4, 763–6.Google Scholar
Caltagarone, J., Rhodes, J., Honer, W. G. & Bowser, R. (1998) Localization of a novel septin protein, hCDCrel-1, in neurons of human brain. Neuroreport, 9 (12), 2907–12.Google Scholar
Carey, A. H., Kelly, D., Halford, S.et al. (1992) Molecular genetic study of the frequency of monosomy 22q11 in DiGeorge syndrome. Am. J. Hum. Genet., 51, 964–70.Google Scholar
Clouthier, D. E., Williams, S. C., Yanagisawa, H.et al. (2000) Signaling pathways crucial for craniofacial development revealed by endothelin-A receptor-deficient mice. Dev Biol, 217 (1), 10–24.Google Scholar
Conti, E., Grifone, N., Sarkozy, A. et al. (2003) DiGeorge subtypes of nonsyndromic conotruncal defects: evidence against a major role of TBX1 Gene. Eur. J. Hum. Genet., 11 (4), 349–51.Google Scholar
Conway, S. J., Henderson, D. J., Kirby, M. L.et al. (1997) Development of a lethal congenital heart defect in the splotch (Pax3) mutant mouse. Cardiovasc. Res., 36, 163–73.Google Scholar
Cote, F., Boisvert, F. M., Grondin, B.et al. (2001) Alternative promoter usage and splicing of ZNF74 multifinger gene produce protein isoforms with a different repressor activity and nuclear partitioning. DNA Cell. Biol., 20 (3), 159–73.Google Scholar
Daw, S. C. M., Taylor, C., Kraman, M.et al. (1996) A common region of 10p deleted in DiGeorge and velo-cardio-facial syndrome. Nat. Genet., 13, 458–60.Google Scholar
Lucia, F., Lorain, S., Scamps, C.et al. (2001) Subnuclear localization and mitotic phosphorylation of HIRA, the human homologue of Saccharomyces cerevisiae transcriptional regulators Hir1p/Hir2p. Biochem. J., 358 (2), 447–55.Google Scholar
Driscoll, D. A. (2001) Prenatal diagnosis of the 22q11.2 deletion syndrome. Genet. Med., 3 (1), 14–18.Google Scholar
Du Montcel, S. T., Mendizabal, H., Ayme, S.et al. (1996) Prevalence of 22q11 microdeletion. J. Med. Genet., 33, 719.Google Scholar
Dunham, I., Shimizu, N., Roe, B. A.et al. (1999) The DNA sequence of human chromosome 22 [see comments] [published erratum appears in Nature 2000, 404 (6780), 904], Nature, 402 (6761), 489–95.Google Scholar
Edelmann, L., Pandita, R., Spiteri, E.et al. (1999a) A common molecular basis for rearrangement disorders on chromosome 22q11. Hum. Mol. Genet., 8, 1157–67.Google Scholar
Edelmann, L., Pandita, R. K., & Morrow, B. E. (1999b) Low-copy repeats mediate the common 3-Mb deletion in patients with velo-cardio-facial syndrome. Am. J. Hum. Genet., 64 (4), 1076–86.Google Scholar
Emanuel, B. S., Budarf, B. S. & Scambler, P. J. (1998) The genetic basis of conotruncal heart defects: the chromosome 22q11.2 deletion. In Rosenthal, N. & Harvey, R., eds., Heart Development. New York: Academic Press, pp. 463–78.
Farrell, M., Stadt, H., Wallis, K.et al. (1999) Persistent truncus arteriosus is associated with decreased expression of HIRA by cardiac neural crest cells in chick embryos. Circulation Research, 84, 127–35.Google Scholar
Feller, S. M. (2001) Crk family adaptors-signalling complex formation and biological roles. Oncogene, 20 (44), 6348–71.Google Scholar
Frank, D. U., Fotheringham, L. K., Brewer, J. A.et al. (2002) An Fgf8 mouse mutant phenocopies human 22q11 deletion syndrome. Development, 129 (19), 4591–603.Google Scholar
Funke, B., Puech, A., Saint-Jore, B.et al. (1998) Isolation and characterization of a human gene containing a nuclear localization signal from the critical region for velo-cardio-facial syndrome on 22q11. Genomics, 53 (2), 146–54.Google Scholar
Galili, N., Epstein, J. A., Leconte, I.et al. (1998) Gscl, a gene within the minimal DiGeorge critical region, is expressed in primordial germ cells and the developing pons. Dev Dyn, 212, 86–93.Google Scholar
Galili, N., Nayak, S., Epstein, J. A. & Buck, C. A. (2000) Rnf4, a RING protein expressed in the developing nervous and reproductive systems, interacts with Gscl, a gene within the DiGeorge critical region. Dev Dyn, 218, 102–11.Google Scholar
Gebhardt, G. S., Devriendt, K., Thoelen, R.et al. (2003) No evidence for a parental inversion polymorphism predisposing to rearrangements at 22q11.2 in the DiGeorge/Velocardiofacial syndrome. Eur. J. Hum. Genet., 11 (2), 109–11.Google Scholar
Gehrmann, T. & Heilmeyer, L. M. Jr. (1998) Phosphatidylinositol 4-kinases. Eur. J. Biochem., 253 (2), 357–70.Google Scholar
Gogos, J. A., Morgan, M., Luine, V.et al. (1998) Catechol-O-methyltransferase-deficient mice exhibit sexually dimorphic changes in catecholamine levels and behavior. Proc. Natl. Acad. Sci. USA, 95 (17), 9991–6.Google Scholar
Gogos, J. A., Santha, M., Takacs, Z.et al. (1999) The gene encoding proline dehydrogenase modulates sensorimotor gating in mice. Nat. Genet., 21 (4), 434–9.Google Scholar
Goldmuntz, E., Fedon, J., Roe, B. & Budarf, M. L. (1997) Molecular characterization of a serine/threonine kinase in the DiGeorge minimal critical region. Gene, 198, 379–86.Google Scholar
Gong, L., Liu, M., Jen, J. & Yeh, E. T. (2000) GNB1L, a gene deleted in the critical region for DiGeorge syndrome on 22q11, encodes a G-protein beta-subunit-like polypeptide (1). Biochim. Biophys. Acta, 1494 (1–2), 185–8.Google Scholar
Gong, W., Emanuel, B. S., Collins, J.et al. (1996) A transcription map of the DiGeorge and velo-cardio-facial syndrome critical region on 22q11. Hum. Mol. Genet., 5, 789–800.Google Scholar
Gong, W., Gottlieb, S., Collins, J.et al. (2001) Mutation analysis of TBX1 in non-deleted patients with features of DGS/VCFS or isolated cardiovascular defects. J. Med. Genet., 38 (12), E45.Google Scholar
Goodship, J., Cross, I., Scambler, P. & Burn, J. (1995) Monozygotic twins with chromosome 22q11 deletion and discordant phenotype. J. Med. Genet., 32, 746–8.Google Scholar
Gottlieb, S., Driscoll, D. A., Punnett, H. H.et al. (1998a) Characterization of 10p deletions suggests two nonoverlapping regions contribute to the DiGeorge syndrome phenotype. Am. J. Hum. Genet., 62, 495–8.Google Scholar
Gottlieb, S., Hanes, S. D., Golden, J. A.et al. (1998b) Goosecoid-like, a gene deleted in DiGeorge and velocardiofacial syndromes, recognizes DNA with a bicoid-like specificity and is expressed in the developing mouse brain. Hum. Mol. Genet., 7 (9), 1497–505.Google Scholar
Graham, A. (2001) The development and evolution of the pharyngeal arches. J. Anat., 199 (1–2), 133–41.Google Scholar
Grondin, B., Cote, F., Bazinet, M.et al. (1997) Direct interaction of the KRAB/Cys2-His2 zinc finger protein ZNF74 with a hyperphosphorylated form of the RNA polymerase II largest subunit. J. Biol. Chem., 272 (44), 27877–85.Google Scholar
Guris, D. L., Fantes, J., Tara, D.et al. (2001) Mice lacking the homologue of the human 22q11.2 gene CRKL phenocopy neurocristopathies of DiGeorge syndrome. Nat. Genet., 27 (3), 293–8.Google Scholar
Halford, S., Lindsay, E., Nayudu, M.et al. (1993a) Low-copy-repeat sequences flank the DiGeorge/velo-cardio-facial syndrome loci at 22q11. Hum. Mol. Genet., 2, 191–6.Google Scholar
Halford, S., Wilson, D. I., Daw, S. C. M.et al. (1993b) Isolation of a gene expressed during early embryogenesis from the region of 22q11 commonly deleted in DiGeorge syndrome. Hum. Mol. Genet., 2, 1577–82.Google Scholar
Hall, C., Nelson, D. M., Ye, X.et al. (2001) HIRA, the human homologue of yeast Hir1p and Hir2p, is a novel cyclin-cdk2 substrate whose expression blocks S-phase progression. Mol. Cell Biol., 21 (5), 1854–65.Google Scholar
Hatchwell, E., Long, F., Wilde, J.et al. (1998) Molecular confirmation of germ line mosaicism for a submicroscopic deletion of chromosome 22q11. Am. J. Med. Genet., 78 (2), 103–6.Google Scholar
Holmes, S. E., Riazi, M. A., Gong, W.et al. (1997) Disruption of the clathrin heavy chain-like gene (CLTCL) associated with features of DGS/VCFS: a balanced (21;22) (p12;q11) translocation. Hum. Mol. Genet., 6, 357–67.Google Scholar
Horb, M. E. & Thomsen, G. H. (1999) Tbx5 is essential for heart development. Development, 126 (8), 1739–51.Google Scholar
Ishii, J., Adachi, H., Aoki, J.et al. (2002) SREC-II, a new member of the scavenger receptor type F family, trans-interacts with SREC-I through its extracellular domain. J. Biol. Chem., 277 (42), 39696–702.Google Scholar
Iwarsson, E., Ahrlund-Richter, L., Inzunza, J.et al. (1998) Preimplantation genetic diagnosis of DiGeorge syndrome. Mol. Hum. Reprod., 4 (9), 871–5.Google Scholar
Jacquet, H., Raux, G., Thibaut, F.et al. (2002) PRODH mutations and hyperprolinemia in a subset of schizophrenic patients. Hum. Mol. Genet., 11 (19), 2243–9.Google Scholar
Jerome, L. A. & Papaioannou, V. E. (2001) DiGeorge syndrome phenotype in mice mutant for the T-box gene. Tbx1. Nat Genet, 27, 286–91.Google Scholar
Kajiwara, K., Nagasawa, H., Shimizu-Nishikawa, K.et al. (1996) Cloning of SEZ-12 encoding seizure-related and membrane bound adhesion protein. Biochem. Biophys. Res. Com., 222, 144–8.Google Scholar
Kimber, W., Hseih, P., Hirotsune, S.et al. (1999) Deletion of 150 kb in the minimal DiGeorge/velocardiofacial syndrome critical region in mouse. Hum. Mol. Genet., 12, 2229–37.Google Scholar
Kirby, M. L. (1999) Contribution of neural crest to heart and vessel morphology. In Harvey, R. P. & Rosenthal, N., eds., Heart Development. New York: Academic Press, pp. 179–94.
Kochilas, L. K., Merscher-Gomez, S., Lu, M. M.et al. (2002) The role of neural crest during cardiac development in a mouse model of DiGeorge syndrome. Dev. Biol., 251, 157–66.Google Scholar
Kurahashi, H., Akagi, K., Inazawa, J.et al. (1995) Isolation and characterization of a novel gene deleted in DiGeorge syndrome. Hum. Mol. Genet., 4, 541–9.Google Scholar
Kurahashi, H., Nakayama, T., Osugi, Y.et al. (1996) Deletion mapping of 22q11 in CATCH22 syndrome: identification of a second critical region. Am. J. Hum. Genet., 58, 1377–81.Google Scholar
Lachman, H. M., Morrow, B., Shprintzen, R.et al. (1996) Association of codon 108/158 catechol-O-methyltransferase gene polymorphism with the psychiatric manifestations of velocardiofacial syndrome. Am. J. Med. Genet., 67, 468–72.Google Scholar
Lammer, E. J., Chen, D. T., Hoar, N. D.et al. (1986) Retinoic acid embryopathy. A new human teratogen and a mechanistic hypothesis. N. Engl. J. Med., 313, 837–41.Google Scholar
Lamorte, L., Royal, I., Naujokas, M. & Park, M. (2002) Crk adapter proteins promote an epithelial-mesenchymal-like transition and are required for HGF-mediated cell spreading and breakdown of epithelial adherens junctions. Mol. Biol. Cell., 13 (5), 1449–61.Google Scholar
Laura, R. P., Witt, A. S., Held, H. A.et al. (2002) The Erbin PDZ domain binds with high affinity and specificity to the carboxyl termini of delta-catenin and ARVCF. J. Biol. Chem., 277(15), 12906–14.Google Scholar
Levy, A., Demczuk, S., Aurias, A.et al. (1995) Interstitial 22q11 deletion excluding the ADU breakpoint in a patient with DGS. Hum. Mol. Genet., 4, 2417–18.Google Scholar
Lichtner, P., Konig, R., Hasegawa, T.et al. (2000) An HDR (hypoparathyroidism, deafness, renal dysplasia) syndrome locus maps distal to the DiGeorge syndrome region on 10p13/14 [In Process Citation]. J. Med. Genet., 37 (1), 33–7.Google Scholar
Lichtner, P., Attie-Bitach, T., Schuffenhauer, S.et al. (2002) Expression and mutation analysis of BRUNOL3, a candidate gene for heart and thymus developmental defects associated with partial monosomy 10p. J. Mol. Med., 80 (7), 431–42.Google Scholar
Lindsay, E. A. & Baldini, A. (1997) A mouse gene (Dgcr6) related to the Drosophila gonadal gene is expressed in early embryogenesis and is the homolog of a human gene deleted in DiGeorge syndrome. Cytogenet. Cell Genet., 79 (3–4), 243–7.Google Scholar
Lindsay, E. A. & Baldini, A.(2001) Recovery from arterial growth delay reduces penetrance of cardiovascular defects in mice deleted for the DiGeorge syndrome region. Hum. Mol. Genet., 10 (9), 997–1002.Google Scholar
Lindsay, E. A., Halford, S., Wadey, R.et al. (1993) Molecular cytogenetic characterisation of the DiGeorge syndrome region using fluorescence in situ hybridisation. Genomics, 17, 403–7.Google Scholar
Lindsay, E. A., Harvey, E. L., Scambler, P. J. & Baldini, A. (1998) ES2, a gene deleted in DiGeorge syndrome, encodes a nuclear protein and is expressed during early mouse development, where it shares an expression domain with a Goosecoid-like gene. Hum. Mol. Genet., 7, 629–35.Google Scholar
Lindsay, E. A., Botta, A., Jurecic, V.et al. (1999) Congenital heart disease in mice deficient for the DiGeorge syndrome region. Nature, 401, 379–83.Google Scholar
Lindsay, E. A., Vitelli, F., Su, H.et al. (2001) Tbx1 haploinsufficiency identified by functional scanning of the DiGeorge syndrome region is the cause of aortic arch defects in mice. Nature, 401, 97–101.Google Scholar
Liu, H., Heath, S. C., Sobin, C.et al. (2002) Genetic variation at the 22q11 PRODH2/DGCR6 locus presents an unusual pattern and increases susceptibility to schizophrenia. Proc. Natl. Acad. Sci. USA, 99 (6), 3717–22.Google Scholar
Lorain, S., Quivy, J.-P., Monier-Gavelle, F.et al. (1998) Core histones and HIRIP3, a novel histone-binding protein, directly interact with the WD repeat protein HIRA. Mol. Cell Biol., 18, 5546–56.Google Scholar
Magnaghi, P., Roberts, C., Lorain, S.et al. (1998) HIRA, a mammalian homologue of Saccharomyces cerevisiae transcriptional co-repressors, interacts with Pax3. Nat. Genet., 20, 74–7.Google Scholar
Malakhov, M. P., Malakhova, O. A., Kim, K. I.et al. (2002) UBP43 (USP18) specifically removes ISG15 from conjugated proteins. J. Biol. Chem., 277 (12), 9976–81.Google Scholar
Mangos, S., Vanderbeld, B., Krawetz, R.et al. (2001) Ran binding protein RanBP1 in zebrafish embryonic development. Mol Reprod Dev, 59 (3), 235–48.Google Scholar
Mariner, D. J., Wang, J. & Reynolds, A. B. (2000) ARVCF localizes to the nucleus and adherens junction and is mutually exclusive with p120 (ctn) in E-cadherin complexes. J. Cell. Sci., 113 (8), 1481–90.Google Scholar
Maynard, T. M., Haskell, G. T., Bhasin, N.et al. (2002) RanBP1, a velocardiofacial/DiGeorge syndrome candidate gene, is expressed at sites of mesenchymal/epithelial induction. Mech. Dev., 111 (1–2), 177–80.Google Scholar
McKerracher, L. & Winton, M. J. (2002) Nogo on the go. Neuron, 36 (3), 345–8.Google Scholar
McKie, J. M., Sutherland, H. F., Harvey, E.et al. (1998) A human gene similar to Drosophila melanogaster peanut maps to the DiGeorge Syndrome region of 22q11. Hum Genet, 101, 6–12.Google Scholar
McQuade, L., Christodoulou, J., Budarf, B.et al. (1999) Patient with a 22q11.2 deletion with no overlap of the minimal DiGeorge syndrome critical region (MDGCR). Am. J. Med. Genet., 86, 27–33.Google Scholar
Merscher, S., Funke, B., Epstein, J. A.et al. (2001) TBX1 is responsible for the cardiovascular defects in velo-cardio-facial/DiGeorge syndrome. Cell, 104, 619–29.Google Scholar
Meyer, H. H., Shorter, J. G., Seemann, J.et al. (2000) A complex of mammalian ufd1 and npl4 links the AAA-ATPase, p97, to ubiquitin and nuclear transport pathways. EMBO J., 19 (10), 2181–92.Google Scholar
Miyamori, H., Takino, T., Kobayashi, Y.et al. (2001) Claudin promotes activation of pro-matrix metalloproteinase-2 mediated by membrane-type matrix metalloproteinases. J. Biol. Chem., 276 (30), 28204–11.Google Scholar
Morita, K., Sasaki, H., Furuse, M. & Tsukita, S. (1999) Endothelial claudin: claudin-5/TMVCF constitutes tight junction strands in endothelial cells. J. Cell Biol., 147 (1), 185–94.Google Scholar
Novelli, G., Amati, F. & Dallapiccola, B. (2000) Individual haploinsufficient loci and the complex phenotype of DiGeorge syndrome. Mol. Med. Today, 6(1), 10–11.Google Scholar
O'Donnell, H., McKeown, C., Gould, C.et al. (1997) Detection of a deletion within 22q11 which has no overlap with the DiGeorge syndrome critical region. Am. J. Hum. Genet., 60, 1544–8.Google Scholar
Osborne, L. R., Li, M., Pober, B.et al. (2001) A 1.5 million-base pair inversion polymorphism in families with Williams-Beuren syndrome. Nat. Genet., 29 (3), 321–5.Google Scholar
Paylor, R., McIlwain, K. L., McAninch, R.et al. (2001) Mice deleted for the DiGeorge/velocardiofacial syndrome region show abnormal sensorimotor gating and learning and memory impairments. Hum. Mol. Genet., 10 (23), 2645–50.Google Scholar
Pfeifer, D., Kist, R., Dewar, K.et al. (1999) Campomelic dysplasia translocation breakpoints are scattered over 1 Mb proximal to SOX9: evidence for an extended control region. Am. J. Hum. Genet., 65 (1), 111–24.Google Scholar
Piotrowski, T. & Nusslein-Volhard, C. (2000) The endoderm plays an important role in patterning the segmented pharyngeal region in zebrafish (Danio rerio). Dev. Biol., 225 (2), 339–56.Google Scholar
Piotrowski, T., Ahn, D. G., Schilling, T. F.et al. (2003) The zebrafish van gogh mutation disrupts Tbx1, which is involved in the DiGeorge deletion syndrome in humans. Development, 130 (20), 5043–52.Google Scholar
Puech, A., Saint-Jore, B., Funke, B.et al. (1997) Comparative mapping of the human 22q11 chromosomal region and the orthologous region in mice reveals complex changes in gene organization. Proc. Natl. Acad. Sci. USA, 94, 14608–13.Google Scholar
Puech, A., Saint-Jore, B., Merscher, S.et al. (2000) Normal cardiovascular development in mice deficient for 16 genes in 550 kb of the velocardiofacial/DiGeorge syndrome region. Proc. Natl. Acad. Sci. USA, 97 (18), 10090–5.Google Scholar
Rape, M., Hoppe, T., Gorr, I.et al. (2001) Mobilization of processed, membrane-tethered SPT23 transcription factor by CDC48 (UFD1/NPL4), a ubiquitin-selective chaperone. Cell, 107 (5), 667–77.Google Scholar
Ravassard, P., Cote, F., Grondin, B.et al. (1999) ZNF74, a gene deleted in DiGeorge syndrome, is expressed in human neural crest-derived tissues and foregut endoderm epithelia. Genomics, 62 (1), 82–5.Google Scholar
Ray-Gallet, D., Quivy, J. P., Scamps, C.et al. (2002) HIRA is critical for a nucleosome assembly pathway independent of DNA synthesis. Mol. Cell, 9 (5), 1091–100.Google Scholar
Roberts, C., Daw, S. C., Halford, S. & Scambler, P. J. (1997) Cloning and developmental expression analysis of chick Hira (Chira), a candidate gene for Di George Syndrome. Hum. Mol. Genet., 6, 237–45.Google Scholar
Roberts, C., Sutherland, H. F., Farmer, H.et al. (2002) Targeted mutagenesis of the Hira gene results in gastrulation defects and patterning abnormalities of mesoendodermal derivatives prior to early embryonic lethality. Mol. Cell. Biol., 22, 2318–28.Google Scholar
Robinson, H. B. Jr. (1975) DiGeorge's or the III-IV pharyngeal pouch syndrome. Pathology and a theory of pathogenesis. Perspect. Ped. Path., 2, 173–206.Google Scholar
Ryan, A. K., Goodship, J. A., Wilson, D. I.et al. (1997) Spectrum of clinical features associated with interstitial chromosome 22q11 deletions: a European collaborative study. J. Med. Genet., 34, 798–804.Google Scholar
Saint-Jore, B., Puech, A., Heyer, J.et al. (1998) Goosecoid-like (Gscl), a candidate gene for velocardiofacial syndrome, is not essential for normal mouse development. Hum. Mol. Genet., 7 (12), 1841–9.Google Scholar
Sandrin-Garcia, P., Macedo, C., Martelli, L. R.et al. (2002) Recurrent 22q11.2 deletion in a sibship suggestive of parental germline mosaicism in velocardiofacial syndrome. Clin. Genet., 61 (5), 380–3.Google Scholar
Scambler, P. J. (2000) The 22q11 deletion syndromes. Hum. Mol. Genet., 9, 2421–6.Google Scholar
Schuffenhauer, S., Lichter, P., Peykar-Derakhshandeh, P.et al. (1998) Deletion mapping on chromosome 10p and definition of a critical region for the second DiGeorge syndrome locus (DGS2). Eur. J. Hum. Genet., 6, 213–25.Google Scholar
Shaikh, T. H., Kurahashi, H., Saitta, S. C.et al. (2000) Chromosome 22-specific low copy repeats and the 22q11.2 deletion syndrome: genomic organization and deletion endpoint analysis. Hum. Mol. Genet., 9 (4), 489–501.Google Scholar
Shaikh, T. H., Kurahashi, H. & Emanuel, B. S. (2001) Evolutionarily conserved low copy repeats (LCRs) in 22q11 mediate deletions, duplications, translocations, and genomic instability: an update and literature review. Genet. Med., 3 (1), 6–13.Google Scholar
Su, Q., Mochida, S., Tian, J. H.et al. (2001) SNAP-29: a general SNARE protein that inhibits SNARE disassembly and is implicated in synaptic transmission. Proc. Natl. Acad. Sci. USA, 98 (24), 14038–43.Google Scholar
Sutherland, H. F., Wadey, R., McKie, J. M.et al. (1996) Identification of a novel transcript disrupted by a balanced translocation associated with DiGeorge syndrome. Am. J. Hum. Genet., 59, 23–31.Google Scholar
Sutherland, H. F., Kim, U.-J. & Scambler, P. J. (1998) Cloning and comparative mapping of the DiGeorge syndrome critical region in the mouse. Genomics, 52, 37–43.Google Scholar
Taddei, I., Morishima, M., Huynh, T. & Lindsay, E. A. (2001) Genetic factors are major determinants of phenotypic variability in a mouse model of the DiGeorge/del22q11 syndromes. Proc. Natl. Acad. Sci. USA, 98 (20), 11428–31.Google Scholar
Takihara, Y., Tomotsune, D., Shirai, M.et al. (1997) Targeted disruption of the mouse homologue of the Drosophila polyhomeotic gene leads to altered anteroposterior patterning and neural crest defects. Development, 124, 3673–82.Google Scholar
Taricani, L., Tejada, M. L. & Young, P. G. (2002) The fission yeast ES2 homologue, Bis1, interacts with the Ish1 stress-responsive nuclear envelope protein. J. Biol. Chem., 277 (12), 10562–72.Google Scholar
Taylor, C., Wadey, R., O'Donnell, H.et al. (1997) Cloning and mapping of murine DGCR2 and its homology to the Sez-12 seizure-related protein. Mamm. Genome, 8, 371–5.Google Scholar
Thomas, T., Kurihara, H., Yamagish, H.et al. (1998) A signaling cascade involving endothelin-1, dHAND, and Msx1 regulates development of neural-crest-derived branchial arch mesenchyme. Development, 125, 3005–14.Google Scholar
Esch, H., Groenen, P., Nesbit, M. A.et al. (2000) GATA3 haplo-insufficiency causes human HDR syndrome. Nature, 406 (6794), 419–22.Google Scholar
Geet, C., Devriendt, K., Eyskens, B.et al. (1998) Velocardiofacial syndrome patients with a heterozygous chromosome 22q11 deletion have giant platelets. Pediatr. Res., 44 (4), 607–11.Google Scholar
Vermot, J., Niederreither, K., Garnier, J. M.et al. (2003) Decreased embryonic retinoic acid synthesis results in a DiGeorge syndrome phenotype in newborn mice. Proc. Natl. Acad. Sci. USA, 100 (4), 1763–8.Google Scholar
Vitelli, F., Morishima, M., Taddei, I.et al. (2002a) Tbx1 mutation causes multiple cardiovascular defects and disrupts neural crest and cranial nerve migratory pathways. Hum. Mol. Genet., 11 (8), 915–22.Google Scholar
Vitelli, F., Taddei, I., Morishima, M.et al. (2002b) A genetic link between Tbx1 and fibroblast growth factor signaling. Development, 129 (19), 4605–11.Google Scholar
Waibler, Z., Schafer, A. & Starzinski-Powitz, A. (2001) mARVCF cellular localisation and binding to cadherins is influenced by the cellular context but not by alternative splicing. J. Cell. Sci., 114 (21), 3873–84.Google Scholar
Wakamiya, M., Lindsay, E. A., Rivera-Perez, J. A.et al. (1998) Functional analysis of Gscl in the pathogenesis of the DiGeorge and velocardiofacial syndromes. Hum. Mol. Genet., 7 (12), 1835–40.Google Scholar
Weitzman, J. B. (2002) Transcriptional territories in the genome. J. Biol., 1 (1), 2.Google Scholar
Wilming, L. G., Snoeren, C. A. S., Rijswijk, A.et al. (1997) The murine homologue of HIRA, a DiGeorge syndrome candidate gene, is expressed in embryonic structures affected in CATCH22 patients. Hum. Mol. Genet., 6, 247–58.Google Scholar
Wilson, D. I., Cross, I. E., Wren, C.et al. (1994) Minimum prevalence of chromosome 22q11 deletions. Am. J. Hum. Genet. 55, A169.Google Scholar
Wilson, T. A., Blethen, S. L., Vallone, A.et al. (1993) DiGeorge anomaly with renal agenesis in infants of mothers with diabetes. Am. J. Med. Genet., 1078, 1082.Google Scholar
Yagi, H., Furutani, Y., Hamada, H.et al. (2003) Role of TBX1 in human del22q11.2 syndrome. Lancet, 362 (9393), 1366–73.Google Scholar
Yamagishi, H., Garg, V., Matsuoka, R.et al. (1999) A molecular pathway revealing a genetic basis for human cardiac and craniofacial defects. Science, 283, 1158–61.Google Scholar
Yamagishi, C., Hierck, B. P., Gittenberger-de Groot, A. C.et al. (2003a) Functional attenuation of Ufd1l, a 22q11.2 deletion syndrome candidate gene, leads to cardiac outflow septation defects in chicken embryos. Pediatr. Res., 53 (4), 546–53.Google Scholar
Yamagishi, H., Maeda, J., Hu, T.et al. (2003b) Tbx1 is regulated by tissue-specific forkhead proteins through a common Sonic hedgehog-responsive enhancer. Genes Dev., 17 (2), 269–81.Google Scholar
Ye, Y., Meyer, H. H. & Rapoport, T. A. (2001) The AAA ATPase Cdc48/p97 and its partners transport proteins from the ER into the cytosol. Nature, 414 (6864), 652–6.Google Scholar
Yoshida, K., Kuo, F., George, E. L.et al. (2001) Requirement of CDC45 for postimplantation mouse development. Mol. Cell. Biol., 21 (14), 4598–603.Google Scholar

Save book to Kindle

To save this book to your Kindle, first ensure [email protected] is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about saving to your Kindle.

Note you can select to save to either the @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be saved to your device when it is connected to wi-fi. ‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

Find out more about the Kindle Personal Document Service.

Available formats
×

Save book to Dropbox

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Dropbox.

Available formats
×

Save book to Google Drive

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Google Drive.

Available formats
×