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. 1996 Mar;33(3):197–202. doi: 10.1136/jmg.33.3.197

Familial Wolf-Hirschhorn syndrome resulting from a cryptic translocation: a clinical and molecular study.

E Reid 1, N Morrison 1, L Barron 1, E Boyd 1, A Cooke 1, D Fielding 1, J L Tolmie 1
PMCID: PMC1051867  PMID: 8728691

Abstract

We present three cousins who have normal karyotypes, despite having clinical features of Wolf-Hirschhorn syndrome. Fluorescence in situ hybridisation techniques confirmed that all three relatives were monosomic for the distal short arm of chromosome 4 and that a cryptic translocation involving chromosomes 4 and 11 was segregating within the family. Segregation analysis indicated that the risk of an affected child being born to a parent carrying the translocation was 15%. Molecular analysis showed that loci D4S111 and D4S115 were not deleted in the proband, thus excluding these loci from the "Wolf-Hirschhorn critical region". Surprisingly, DNA studies also suggested that the translocation breakpoint on chromosome 4 was within the region of a preexisting paracentric inversion.

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Selected References

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  1. Allitto B. A., McClatchey A. I., Barnes G., Altherr M., Wasmuth J., Frischauf A. M., MacDonald M. E., Gusella J. Assay by polymerase chain reaction (PCR) of multi-allele polymorphisms in the Huntington's disease region of chromosome 4. Mol Cell Probes. 1992 Dec;6(6):513–520. doi: 10.1016/0890-8508(92)90048-3. [DOI] [PubMed] [Google Scholar]
  2. Altherr M. R., Bengtsson U., Elder F. F., Ledbetter D. H., Wasmuth J. J., McDonald M. E., Gusella J. F., Greenberg F. Molecular confirmation of Wolf-Hirschhorn syndrome with a subtle translocation of chromosome 4. Am J Hum Genet. 1991 Dec;49(6):1235–1242. [PMC free article] [PubMed] [Google Scholar]
  3. Altherr M. R., Gusella J. F., Wasmuth J. J., Kummer M. A., McKercher S. W., Johnson V. P. Molecular detection of a 4p deletion using PCR-based polymorphisms: a technique for the rapid detection of the Wolf-Hirschhorn syndrome. Am J Med Genet. 1992 Nov 1;44(4):449–454. doi: 10.1002/ajmg.1320440413. [DOI] [PubMed] [Google Scholar]
  4. Batista D. A., Pai G. S., Stetten G. Molecular analysis of a complex chromosomal rearrangement and a review of familial cases. Am J Med Genet. 1994 Nov 15;53(3):255–263. doi: 10.1002/ajmg.1320530311. [DOI] [PubMed] [Google Scholar]
  5. Bonthron D. T., Smith S. J., Fantes J., Gosden C. M. De novo microdeletion on an inherited Robertsonian translocation chromosome: a cause for dysmorphism in the apparently balanced translocation carrier. Am J Hum Genet. 1993 Sep;53(3):629–637. [PMC free article] [PubMed] [Google Scholar]
  6. Carter N. P., Ferguson-Smith M. A., Perryman M. T., Telenius H., Pelmear A. H., Leversha M. A., Glancy M. T., Wood S. L., Cook K., Dyson H. M. Reverse chromosome painting: a method for the rapid analysis of aberrant chromosomes in clinical cytogenetics. J Med Genet. 1992 May;29(5):299–307. doi: 10.1136/jmg.29.5.299. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Estabrooks L. L., Lamb A. N., Aylsworth A. S., Callanan N. P., Rao K. W. Molecular characterisation of chromosome 4p deletions resulting in Wolf-Hirschhorn syndrome. J Med Genet. 1994 Feb;31(2):103–107. doi: 10.1136/jmg.31.2.103. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Estabrooks L. L., Rao K. W., Driscoll D. A., Crandall B. F., Dean J. C., Ikonen E., Korf B., Aylsworth A. S. Preliminary phenotypic map of chromosome 4p16 based on 4p deletions. Am J Med Genet. 1995 Jul 17;57(4):581–586. doi: 10.1002/ajmg.1320570413. [DOI] [PubMed] [Google Scholar]
  9. Fagan K., Colley P., Partington M. A practical application of fluorescent in situ hybridization to the Wolf-Hirschhorn syndrome. Pediatrics. 1994 May;93(5):826–827. [PubMed] [Google Scholar]
  10. Flint J., Wilkie A. O., Buckle V. J., Winter R. M., Holland A. J., McDermid H. E. The detection of subtelomeric chromosomal rearrangements in idiopathic mental retardation. Nat Genet. 1995 Feb;9(2):132–140. doi: 10.1038/ng0295-132. [DOI] [PubMed] [Google Scholar]
  11. Francomano C. A., Ortiz de Luna R. I., Hefferon T. W., Bellus G. A., Turner C. E., Taylor E., Meyers D. A., Blanton S. H., Murray J. C., McIntosh I. Localization of the achondroplasia gene to the distal 2.5 Mb of human chromosome 4p. Hum Mol Genet. 1994 May;3(5):787–792. doi: 10.1093/hmg/3.5.787. [DOI] [PubMed] [Google Scholar]
  12. Gandelman K. Y., Gibson L., Meyn M. S., Yang-Feng T. L. Molecular definition of the smallest region of deletion overlap in the Wolf-Hirschhorn syndrome. Am J Hum Genet. 1992 Sep;51(3):571–578. [PMC free article] [PubMed] [Google Scholar]
  13. Garson J. A., van den Berghe J. A., Kemshead J. T. Novel non-isotopic in situ hybridization technique detects small (1 Kb) unique sequences in routinely G-banded human chromosomes: fine mapping of N-myc and beta-NGF genes. Nucleic Acids Res. 1987 Jun 25;15(12):4761–4770. doi: 10.1093/nar/15.12.4761. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Goodship J., Curtis A., Cross I., Brown J., Emslie J., Wolstenholme J., Bhattacharya S., Burn J. A submicroscopic translocation, t(4;10), responsible for recurrent Wolf-Hirschhorn syndrome identified by allele loss and fluorescent in situ hybridisation. J Med Genet. 1992 Jul;29(7):451–454. [PMC free article] [PubMed] [Google Scholar]
  15. Lamb J., Wilkie A. O., Harris P. C., Buckle V. J., Lindenbaum R. H., Barton N. J., Reeders S. T., Weatherall D. J., Higgs D. R. Detection of breakpoints in submicroscopic chromosomal translocation, illustrating an important mechanism for genetic disease. Lancet. 1989 Oct 7;2(8667):819–824. doi: 10.1016/s0140-6736(89)92995-4. [DOI] [PubMed] [Google Scholar]
  16. MacDonald M. E., Anderson M. A., Gilliam T. C., Tranejaerg L., Carpenter N. J., Magenis E., Hayden M. R., Healey S. T., Bonner T. I., Gusella J. F. A somatic cell hybrid panel for localizing DNA segments near the Huntington's disease gene. Genomics. 1987 Sep;1(1):29–34. doi: 10.1016/0888-7543(87)90101-7. [DOI] [PubMed] [Google Scholar]
  17. Pettenati M. J., Hayworth R., Cox K., Rao P. N. Prenatal detection of cri du chat syndrome on uncultured amniocytes using fluorescence in situ hybridization (FISH). Clin Genet. 1994 Jan;45(1):17–20. doi: 10.1111/j.1399-0004.1994.tb03983.x. [DOI] [PubMed] [Google Scholar]
  18. Pinkel D., Straume T., Gray J. W. Cytogenetic analysis using quantitative, high-sensitivity, fluorescence hybridization. Proc Natl Acad Sci U S A. 1986 May;83(9):2934–2938. doi: 10.1073/pnas.83.9.2934. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Tommerup N., Aagaard L., Lund C. L., Boel E., Baxendale S., Bates G. P., Lehrach H., Vissing H. A zinc-finger gene ZNF141 mapping at 4p16.3/D4S90 is a candidate gene for the Wolf-Hirschhorn (4p-) syndrome. Hum Mol Genet. 1993 Oct;2(10):1571–1575. doi: 10.1093/hmg/2.10.1571. [DOI] [PubMed] [Google Scholar]
  20. Tranebjaerg L., Petersen A., Hove K., Rehder H., Mikkelsen M. Clinical and cytogenetic studies in a large (4;8) translocation family with pre- and postnatal Wolf syndrome. Ann Genet. 1984;27(4):224–229. [PubMed] [Google Scholar]
  21. Warner J. P., Barron L. H., Brock D. J. A new polymerase chain reaction (PCR) assay for the trinucleotide repeat that is unstable and expanded on Huntington's disease chromosomes. Mol Cell Probes. 1993 Jun;7(3):235–239. doi: 10.1006/mcpr.1993.1034. [DOI] [PubMed] [Google Scholar]
  22. Wolf U., Reinwein H., Porsch R., Schröter R., Baitsch H. Defizienz an den kuzen Armen eins Chromosoms Nr. 4. Humangenetik. 1965;1(5):397–413. [PubMed] [Google Scholar]
  23. Xiang K., Karam J. H., Bell G. I. BamHI RFLP at the insulin-like growth factor II (IGF2) locus on chromosome 11. Nucleic Acids Res. 1987 Sep 25;15(18):7655–7655. doi: 10.1093/nar/15.18.7655. [DOI] [PMC free article] [PubMed] [Google Scholar]

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