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PMID: 7762562 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Molecular definition of the 22q11 deletions in velo-cardio-facial syndrome.

American journal of human genetics ·Vol. 56 ·No. 6 ·1995-06-00 ·Pages 1391-403

Morrow B, Goldberg R, Carlson C, Das Gupta R, Sirotkin H, Collins J, Dunham I, O'Donnell H, Scambler P, Shprintzen R

Abstract

Velo-cardio-facial syndrome (VCFS) is a common genetic disorder among individuals with cleft palate and is associated with hemizygous deletions in human chromosome 22q11. Toward the molecular definition of the deletions, we constructed a physical map of 22q11 in the form of overlapping YACs. The physical map covers > 9 cM of genetic distance, estimated to span 5 Mb of DNA, and contains a total of 64 markers. Eleven highly polymorphic short tandem-repeat polymorphic (STRP) markers were placed on the physical map, and 10 of these were unambiguously ordered. The 11 polymorphic markers were used to type the DNA from a total of 61 VCFS patients and 49 unaffected relatives. Comparison of levels of heterozygosity of these markers in VCFS patients and their unaffected relatives revealed that four of these markers are commonly hemizygous among VCFS patients. To confirm these results and to define further the breakpoints in VCFS patients, 15 VCFS individuals and their unaffected parents were genotyped for the 11 STRP markers. Haplotypes generated from this study revealed that 82% of the patients have deletions that can be defined by the STRP markers. The results revealed that all patients who have a deletion share a common proximal breakpoint, while there are two distinct distal breakpoints. Markers D22S941 and D22S944 appear to be consistently hemizygous in patients with deletions. Both of these markers are located on a single nonchimeric YAC that is 400 kb long. The results also show that the parental origin of the deleted chromosome does not have any effect on the phenotypic manifestation.

MeSH Terms
Abnormalities, Multiple/etiology,genetics Base Sequence Chromosome Mapping Chromosomes, Artificial, Yeast Chromosomes, Human, Pair 22/genetics DiGeorge Syndrome/etiology,genetics Face/abnormalities Female Genetic Markers Genotype Heart Defects, Congenital/etiology,genetics Humans Male Molecular Sequence Data Mouth Abnormalities/etiology,genetics Polymorphism, Genetic Sequence Deletion Syndrome
Chemicals
Genetic Markers
Authors & Affiliations
10 authors, click to expand affiliations / ORCID
Morrow B
Department of Molecular Genetics, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
Goldberg R
Carlson C
Das Gupta R
Sirotkin H
Collins J
Dunham I
O'Donnell H
Scambler P
Shprintzen R
References (52)
52 references, click to expand
  1. Craniofacial morphology in the velo-cardio-facial syndrome.
    J Craniofac Genet Dev Biol. 1984;4(1):39-45 PMID: 6736220
  2. Psychotic illness in patients diagnosed with velo-cardio-facial syndrome and their relatives.
    J Nerv Ment Dis. 1994 Aug;182(8):476-8 PMID: 8040660
  3. Retrospective diagnoses of previously missed syndromic disorders among 1,000 patients with cleft lip, cleft palate, or both.
    Birth Defects Orig Artic Ser. 1985;21(2):85-92 PMID: 3840043
  4. Velo-cardio-facial syndrome: language and psychological profiles.
    J Craniofac Genet Dev Biol. 1985;5(3):259-66 PMID: 4044789
  5. Cardiovascular anomalies in DiGeorge syndrome and importance of neural crest as a possible pathogenetic factor.
    Am J Cardiol. 1986 Jul 1;58(1):133-7 PMID: 3728313
  6. DiGeorge syndrome and 22q11 rearrangements.
    Hum Genet. 1986 Oct;74(2):206 PMID: 3770751
  7. Adenoid hypoplasia in the velo-cardio-facial syndrome.
    J Craniofac Genet Dev Biol. 1987;7(1):23-6 PMID: 3597719
  8. Duplication of the bcr and gamma-glutamyl transpeptidase genes.
    Nucleic Acids Res. 1988 Aug 25;16(16):8045-56 PMID: 2901712
  9. A genetic linkage map of the long arm of human chromosome 22.
    Genomics. 1989 Jan;4(1):1-6 PMID: 2563348
  10. Angelman and Prader-Willi syndromes share a common chromosome 15 deletion but differ in parental origin of the deletion.
    Am J Med Genet. 1989 Feb;32(2):285-90 PMID: 2564739
  11. Isolation of single-copy human genes from a library of yeast artificial chromosome clones.
    Science. 1989 Jun 16;244(4910):1348-51 PMID: 2544027
  12. Genetic imprinting suggested by maternal heterodisomy in nondeletion Prader-Willi syndrome.
    Nature. 1989 Nov 16;342(6247):281-5 PMID: 2812027
  13. A novel, rapid method for the isolation of terminal sequences from yeast artificial chromosome (YAC) clones.
    Nucleic Acids Res. 1990 May 25;18(10):2887-90 PMID: 2161516
  14. Localization of 27 DNA markers to the region of human chromosome 22q11-pter deleted in patients with the DiGeorge syndrome and duplicated in the der22 syndrome.
    Genomics. 1990 Jul;7(3):299-306 PMID: 2365351
  15. Yeast artificial chromosome libraries containing large inserts from mouse and human DNA.
    Proc Natl Acad Sci U S A. 1991 May 15;88(10):4123-7 PMID: 2034658
  16. Microdeletions within 22q11 associated with sporadic and familial DiGeorge syndrome.
    Genomics. 1991 May;10(1):201-6 PMID: 2045103
  17. Isolation and regional localization of 35 unique anonymous DNA markers for human chromosome 22.
    Genomics. 1991 Aug;10(4):996-1002 PMID: 1680800
  18. Velocardiofacial (Shprintzen) syndrome: an important syndrome for the dysmorphologist to recognise.
    J Med Genet. 1991 Sep;28(9):596-604 PMID: 1956057
  19. A genetic etiology for DiGeorge syndrome: consistent deletions and microdeletions of 22q11.
    Am J Hum Genet. 1992 May;50(5):924-33 PMID: 1349199
  20. Velo-cardio-facial syndrome associated with chromosome 22 deletions encompassing the DiGeorge locus.
    Lancet. 1992 May 9;339(8802):1138-9 PMID: 1349369
  21. Velo-cardio-facial syndrome associated with ventricular septal defect, pulmonary atresia, and hypoplastic pulmonary arteries.
    Pediatrics. 1992 May;89(5 Pt 1):915-9 PMID: 1374552
  22. Mapping the whole human genome by fingerprinting yeast artificial chromosomes.
    Cell. 1992 Sep 18;70(6):1059-68 PMID: 1525822
  23. A prospective cytogenetic study of 36 cases of DiGeorge syndrome.
    Am J Hum Genet. 1992 Nov;51(5):957-63 PMID: 1415264
  24. Deletions and microdeletions of 22q11.2 in velo-cardio-facial syndrome.
    Am J Med Genet. 1992 Sep 15;44(2):261-8 PMID: 1360769
  25. A panel of human chromosome 22-specific sequence tagged sites.
    Genomics. 1992 Dec;14(4):1098-103 PMID: 1478652
  26. Isolation and characterization of 25 unique DNA markers for human chromosome 22.
    Genomics. 1993 Jan;15(1):206-8 PMID: 8094368
  27. Twelve new polymorphic microsatellites on human chromosome 22.
    Genomics. 1993 Jan;15(1):57-61 PMID: 8432551
  28. Confirmation that the velo-cardio-facial syndrome is associated with haplo-insufficiency of genes at chromosome 22q11.
    Am J Med Genet. 1993 Feb 1;45(3):308-12 PMID: 8434616
  29. Velo-cardio-facial syndrome: a review of 120 patients.
    Am J Med Genet. 1993 Feb 1;45(3):313-9 PMID: 8434617
  30. Isolation of chromosome 21-specific yeast artificial chromosomes from a total human genome library.
    Nat Genet. 1992 Jun;1(3):222-5 PMID: 1303240
  31. Low-copy-number repeat sequences flank the DiGeorge/velo-cardio-facial syndrome loci at 22q11.
    Hum Mol Genet. 1993 Feb;2(2):191-6 PMID: 8499906
  32. Velo-cardio-facial syndrome and psychotic disorders: implications for psychiatric genetics.
    Am J Med Genet. 1994 Jun 15;54(2):107-12 PMID: 8074160
  33. The 1993-94 Généthon human genetic linkage map.
    Nat Genet. 1994 Jun;7(2 Spec No):246-339 PMID: 7545953
  34. Isolation and regional mapping of 110 chromosome 22 STSs.
    Genomics. 1994 Dec;24(3):588-92 PMID: 7713513
  35. Neural crest and normal development: a new perspective.
    Anat Rec. 1984 May;209(1):1-6 PMID: 6731866
  36. A new syndrome involving cleft palate, cardiac anomalies, typical facies, and learning disabilities: velo-cardio-facial syndrome.
    Cleft Palate J. 1978 Jan;15(1):56-62 PMID: 272242
  37. Cardiac malformations in the velocardiofacial syndrome.
    Am J Cardiol. 1980 Oct;46(4):643-8 PMID: 7416023
  38. Deletions of chromosome 15 as a cause of the Prader-Willi syndrome.
    N Engl J Med. 1981 Feb 5;304(6):325-9 PMID: 7442771
  39. The velo-cardio-facial syndrome: a clinical and genetic analysis.
    Pediatrics. 1981 Feb;67(2):167-72 PMID: 7243439
  40. A deletion in chromosome 22 can cause DiGeorge syndrome.
    Hum Genet. 1981;57(3):253-6 PMID: 7250965
  41. The association of the DiGeorge anomalad with partial monosomy of chromosome 22.
    J Pediatr. 1982 Aug;101(2):197-200 PMID: 7097410
  42. Neural crest cells contribute to normal aorticopulmonary septation.
    Science. 1983 Jun 3;220(4601):1059-61 PMID: 6844926
  43. Chemically induced congenital thymic dysgenesis in the rat: a model of the DiGeorge syndrome.
    Clin Immunol Immunopathol. 1983 Jul;28(1):128-34 PMID: 6872357
  44. Dependence of thymus development on derivatives of the neural crest.
    Science. 1984 Feb 3;223(4635):498-500 PMID: 6606851
  45. Mapping of human gamma-glutamyl transpeptidase genes on chromosome 22 and other human autosomes.
    Genomics. 1993 Aug;17(2):299-305 PMID: 8104871
  46. Prevalence of 22q11 microdeletions in DiGeorge and velocardiofacial syndromes: implications for genetic counselling and prenatal diagnosis.
    J Med Genet. 1993 Oct;30(10):813-7 PMID: 8230155
  47. Physical mapping by FISH of the DiGeorge critical region (DGCR): involvement of the region in familial cases.
    Am J Hum Genet. 1993 Dec;53(6):1239-49 PMID: 8250039
  48. Isolation of a gene expressed during early embryogenesis from the region of 22q11 commonly deleted in DiGeorge syndrome.
    Hum Mol Genet. 1993 Oct;2(10):1577-82 PMID: 8268909
  49. A microsatellite-based multipoint index map of human chromosome 22.
    Genomics. 1993 Nov;18(2):329-39 PMID: 8288236
  50. Isolation of a putative transcriptional regulator from the region of 22q11 deleted in DiGeorge syndrome, Shprintzen syndrome and familial congenital heart disease.
    Hum Mol Genet. 1993 Dec;2(12):2099-107 PMID: 8111380
  51. Twenty-one polymorphic markers from human chromosome 12 for integration of genetic and physical maps.
    Genomics. 1994 Jan 15;19(2):341-9 PMID: 8188264
  52. Male-to-male transmission of the velo-cardio-facial syndrome: a case report and review of 60 cases.
    J Craniofac Genet Dev Biol. 1985;5(2):175-80 PMID: 4019731
Article Info
Journal
American journal of human genetics
Abbr.
Am J Hum Genet
ISSN
0002-9297
Published
1995-06-00
Pages
1391-403
Language
English
Region
United States
NLM ID
0370475
PMCID
PMC1801093
Subset
IM
Grants
NICHD NIH HHS · R01HD31601 · United States
External Links
PubMed source PMC Full Text View journal details
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