Skip to main content
NCBI home page
Journal of Medical Genetics logoLink to Journal of Medical Genetics
. 1995 Jul;32(7):531–536. doi: 10.1136/jmg.32.7.531

Chromosome 13q deletion with Waardenburg syndrome: further evidence for a gene involved in neural crest function on 13q.

G Van Camp 1, M N Van Thienen 1, I Handig 1, B Van Roy 1, V S Rao 1, A Milunsky 1, A P Read 1, C T Baldwin 1, L A Farrer 1, M Bonduelle 1, et al.
PMCID: PMC1050545  PMID: 7562965

Abstract

Waardenburg syndrome (WS) is an autosomal dominant disorder characterised by pigmentary abnormalities and sensorineural deafness. It is subcategorised into type 1 (WS1) and type 2 (WS2) on the basis of the presence (WS1) or absence (WS2) of dystopia canthorum. WS1 is always caused by mutations in the PAX3 gene, whereas WS2 is caused by mutations in the microphthalmia (MITF) gene in some but not all families. An association of WS symptoms with Hirschsprung disease (HSCR) has been reported in many families. We report here a patient with characteristics of WS2 and a de novo interstitial deletion of chromosome 13q. We also describe a family with two sibs who have both WS2 and HSCR. In this family, all possible genes for WS and HSCR, but not chromosome 13q, could be excluded. As an association between chromosome 13q and HSCR/WS has been reported previously, these data suggest that there is a gene on chromosome 13q that is responsible for WS or HSCR or both.

Full text

PDF
531

Images in this article

532Image
on p.532
533Image
on p.533

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Ambani L. M. Waardenburg and Hirschsprung syndromes. J Pediatr. 1983 May;102(5):802–802. doi: 10.1016/s0022-3476(83)80267-4. [DOI] [PubMed] [Google Scholar]
  2. Arias S. Genetic heterogeneity in the Waardenburg syndrome. Birth Defects Orig Artic Ser. 1971 Mar;07(4):87–101. [PubMed] [Google Scholar]
  3. Asher J. H., Jr, Morell R., Friedman T. B. Waardenburg syndrome (WS): the analysis of a single family with a WS1 mutation showing linkage to RFLP markers on human chromosome 2q. Am J Hum Genet. 1991 Jan;48(1):43–52. [PMC free article] [PubMed] [Google Scholar]
  4. Baldwin C. T., Hoth C. F., Amos J. A., da-Silva E. O., Milunsky A. An exonic mutation in the HuP2 paired domain gene causes Waardenburg's syndrome. Nature. 1992 Feb 13;355(6361):637–638. doi: 10.1038/355637a0. [DOI] [PubMed] [Google Scholar]
  5. Bottani A., Xie Y. G., Binkert F., Schinzel A. A case of Hirschsprung disease with a chromosome 13 microdeletion, del(13)(q32.3q33.2): potential mapping of one disease locus. Hum Genet. 1991 Oct;87(6):748–750. doi: 10.1007/BF00201741. [DOI] [PubMed] [Google Scholar]
  6. Bowcock A., Osborne-Lawrence S., Barnes R., Chakravarti A., Washington S., Dunn C. Microsatellite polymorphism linkage map of human chromosome 13q. Genomics. 1993 Feb;15(2):376–386. doi: 10.1006/geno.1993.1071. [DOI] [PubMed] [Google Scholar]
  7. Bowcock A. Report of the First International Workshop on Human Chromosome 13 Mapping. Dallas, Texas, September 21-22, 1992. Cytogenet Cell Genet. 1993;62(2-3):89–107. doi: 10.1159/000133450. [DOI] [PubMed] [Google Scholar]
  8. Brown S., Gersen S., Anyane-Yeboa K., Warburton D. Preliminary definition of a "critical region" of chromosome 13 in q32: report of 14 cases with 13q deletions and review of the literature. Am J Med Genet. 1993 Jan 1;45(1):52–59. doi: 10.1002/ajmg.1320450115. [DOI] [PubMed] [Google Scholar]
  9. Buetow K. H., Weber J. L., Ludwigsen S., Scherpbier-Heddema T., Duyk G. M., Sheffield V. C., Wang Z., Murray J. C. Integrated human genome-wide maps constructed using the CEPH reference panel. Nat Genet. 1994 Apr;6(4):391–393. doi: 10.1038/ng0494-391. [DOI] [PubMed] [Google Scholar]
  10. Cuticchia A. J., Fasman K. H., Kingsbury D. T., Robbins R. J., Pearson P. L. The GDB human genome data base anno 1993. Nucleic Acids Res. 1993 Jul 1;21(13):3003–3006. doi: 10.1093/nar/21.13.3003. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Dow E., Cross S., Wolgemuth D. J., Lyonnet S., Mulligan L. M., Mascari M., Ladda R., Williamson R. Second locus for Hirschsprung disease/Waardenburg syndrome in a large Mennonite kindred. Am J Med Genet. 1994 Oct 15;53(1):75–80. doi: 10.1002/ajmg.1320530116. [DOI] [PubMed] [Google Scholar]
  12. Edery P., Lyonnet S., Mulligan L. M., Pelet A., Dow E., Abel L., Holder S., Nihoul-Fékété C., Ponder B. A., Munnich A. Mutations of the RET proto-oncogene in Hirschsprung's disease. Nature. 1994 Jan 27;367(6461):378–380. doi: 10.1038/367378a0. [DOI] [PubMed] [Google Scholar]
  13. Epstein D. J., Vekemans M., Gros P. Splotch (Sp2H), a mutation affecting development of the mouse neural tube, shows a deletion within the paired homeodomain of Pax-3. Cell. 1991 Nov 15;67(4):767–774. doi: 10.1016/0092-8674(91)90071-6. [DOI] [PubMed] [Google Scholar]
  14. Farrer L. A., Arnos K. S., Asher J. H., Jr, Baldwin C. T., Diehl S. R., Friedman T. B., Greenberg J., Grundfast K. M., Hoth C., Lalwani A. K. Locus heterogeneity for Waardenburg syndrome is predictive of clinical subtypes. Am J Hum Genet. 1994 Oct;55(4):728–737. [PMC free article] [PubMed] [Google Scholar]
  15. Farrer L. A., Grundfast K. M., Amos J., Arnos K. S., Asher J. H., Jr, Beighton P., Diehl S. R., Fex J., Foy C., Friedman T. B. Waardenburg syndrome (WS) type I is caused by defects at multiple loci, one of which is near ALPP on chromosome 2: first report of the WS consortium. Am J Hum Genet. 1992 May;50(5):902–913. [PMC free article] [PubMed] [Google Scholar]
  16. Foy C., Newton V., Wellesley D., Harris R., Read A. P. Assignment of the locus for Waardenburg syndrome type I to human chromosome 2q37 and possible homology to the Splotch mouse. Am J Hum Genet. 1990 Jun;46(6):1017–1023. [PMC free article] [PubMed] [Google Scholar]
  17. Fried K., Beer S. Waardenburg's syndrome and Hirschsprung's disease in the same patient. Clin Genet. 1980 Jul;18(1):91–92. [PubMed] [Google Scholar]
  18. Goodman R. M., Lewithal I., Solomon A., Klein D. Upper limb involvement in the Klein-Waardenburg syndrome. Am J Med Genet. 1982 Apr;11(4):425–433. doi: 10.1002/ajmg.1320110407. [DOI] [PubMed] [Google Scholar]
  19. Hosoda K., Hammer R. E., Richardson J. A., Baynash A. G., Cheung J. C., Giaid A., Yanagisawa M. Targeted and natural (piebald-lethal) mutations of endothelin-B receptor gene produce megacolon associated with spotted coat color in mice. Cell. 1994 Dec 30;79(7):1267–1276. doi: 10.1016/0092-8674(94)90017-5. [DOI] [PubMed] [Google Scholar]
  20. Hoth C. F., Milunsky A., Lipsky N., Sheffer R., Clarren S. K., Baldwin C. T. Mutations in the paired domain of the human PAX3 gene cause Klein-Waardenburg syndrome (WS-III) as well as Waardenburg syndrome type I (WS-I). Am J Hum Genet. 1993 Mar;52(3):455–462. [PMC free article] [PubMed] [Google Scholar]
  21. Hughes A. E., Newton V. E., Liu X. Z., Read A. P. A gene for Waardenburg syndrome type 2 maps close to the human homologue of the microphthalmia gene at chromosome 3p12-p14.1. Nat Genet. 1994 Aug;7(4):509–512. doi: 10.1038/ng0894-509. [DOI] [PubMed] [Google Scholar]
  22. Hughes A. E. Optimization of microsatellite analysis for genetic mapping. Genomics. 1993 Feb;15(2):433–434. doi: 10.1006/geno.1993.1083. [DOI] [PubMed] [Google Scholar]
  23. Ishikiriyama S., Tonoki H., Shibuya Y., Chin S., Harada N., Abe K., Niikawa N. Waardenburg syndrome type I in a child with de novo inversion (2)(q35q37.3). Am J Med Genet. 1989 Aug;33(4):505–507. doi: 10.1002/ajmg.1320330419. [DOI] [PubMed] [Google Scholar]
  24. Kiss P., Osztovics M. Association of 13q deletion and Hirschsprung's disease. J Med Genet. 1989 Dec;26(12):793–794. doi: 10.1136/jmg.26.12.793. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Klein D. Historical background and evidence for dominant inheritance of the Klein-Waardenburg syndrome (type III). Am J Med Genet. 1983 Feb;14(2):231–239. doi: 10.1002/ajmg.1320140205. [DOI] [PubMed] [Google Scholar]
  26. Lamont M. A., Fitchett M., Dennis N. R. Interstitial deletion of distal 13q associated with Hirschsprung's disease. J Med Genet. 1989 Feb;26(2):100–104. doi: 10.1136/jmg.26.2.100. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Lane P. W. Association of megacolon with two recessive spotting genes in the mouse. J Hered. 1966 Jan-Feb;57(1):29–31. doi: 10.1093/oxfordjournals.jhered.a107457. [DOI] [PubMed] [Google Scholar]
  28. Lathrop G. M., Lalouel J. M. Easy calculations of lod scores and genetic risks on small computers. Am J Hum Genet. 1984 Mar;36(2):460–465. [PMC free article] [PubMed] [Google Scholar]
  29. Meire F., Standaert L., De Laey J. J., Zeng L. H. Waardenburg syndrome, Hirschsprung megacolon, and Marcus Gunn ptosis. Am J Med Genet. 1987 Jul;27(3):683–686. doi: 10.1002/ajmg.1320270322. [DOI] [PubMed] [Google Scholar]
  30. Metallinos D. L., Oppenheimer A. J., Rinchik E. M., Russell L. B., Dietrich W., Tilghman S. M. Fine structure mapping and deletion analysis of the murine piebald locus. Genetics. 1994 Jan;136(1):217–223. doi: 10.1093/genetics/136.1.217. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Morell R., Friedman T. B., Moeljopawiro S., Hartono, Soewito, Asher J. H., Jr A frameshift mutation in the HuP2 paired domain of the probable human homolog of murine Pax-3 is responsible for Waardenburg syndrome type 1 in an Indonesian family. Hum Mol Genet. 1992 Jul;1(4):243–247. doi: 10.1093/hmg/1.4.243. [DOI] [PubMed] [Google Scholar]
  32. Omenn G. S., McKusick V. A. The association of Waardenburg syndrome and Hirschsprung megacolon. Am J Med Genet. 1979;3(3):217–223. doi: 10.1002/ajmg.1320030302. [DOI] [PubMed] [Google Scholar]
  33. Ott J. Estimation of the recombination fraction in human pedigrees: efficient computation of the likelihood for human linkage studies. Am J Hum Genet. 1974 Sep;26(5):588–597. [PMC free article] [PubMed] [Google Scholar]
  34. Palmer C. G., Heerema N., Bull M. Deletions in chromosome 2 and fragile sites. Am J Med Genet. 1990 Jun;36(2):214–218. doi: 10.1002/ajmg.1320360215. [DOI] [PubMed] [Google Scholar]
  35. Pasteris N. G., Trask B. J., Sheldon S., Gorski J. L. Discordant phenotype of two overlapping deletions involving the PAX3 gene in chromosome 2q35. Hum Mol Genet. 1993 Jul;2(7):953–959. doi: 10.1093/hmg/2.7.953. [DOI] [PubMed] [Google Scholar]
  36. Petrukhin K. E., Speer M. C., Cayanis E., Bonaldo M. F., Tantravahi U., Soares M. B., Fischer S. G., Warburton D., Gilliam T. C., Ott J. A microsatellite genetic linkage map of human chromosome 13. Genomics. 1993 Jan;15(1):76–85. doi: 10.1006/geno.1993.1012. [DOI] [PubMed] [Google Scholar]
  37. Puffenberger E. G., Hosoda K., Washington S. S., Nakao K., deWit D., Yanagisawa M., Chakravart A. A missense mutation of the endothelin-B receptor gene in multigenic Hirschsprung's disease. Cell. 1994 Dec 30;79(7):1257–1266. doi: 10.1016/0092-8674(94)90016-7. [DOI] [PubMed] [Google Scholar]
  38. Puffenberger E. G., Kauffman E. R., Bolk S., Matise T. C., Washington S. S., Angrist M., Weissenbach J., Garver K. L., Mascari M., Ladda R. Identity-by-descent and association mapping of a recessive gene for Hirschsprung disease on human chromosome 13q22. Hum Mol Genet. 1994 Aug;3(8):1217–1225. doi: 10.1093/hmg/3.8.1217. [DOI] [PubMed] [Google Scholar]
  39. Romeo G., Ronchetto P., Luo Y., Barone V., Seri M., Ceccherini I., Pasini B., Bocciardi R., Lerone M., Käriäinen H. Point mutations affecting the tyrosine kinase domain of the RET proto-oncogene in Hirschsprung's disease. Nature. 1994 Jan 27;367(6461):377–378. doi: 10.1038/367377a0. [DOI] [PubMed] [Google Scholar]
  40. Scheres J. M., Merkx G. F., Hustinx T. W. Prometaphase banding of human chromosomes with basic fuchsin. Hum Genet. 1982;61(1):8–11. doi: 10.1007/BF00291322. [DOI] [PubMed] [Google Scholar]
  41. Shah K. N., Dalal S. J., Desai M. P., Sheth P. N., Joshi N. C., Ambani L. M. White forelock, pigmentary disorder of irides, and long segment Hirschsprung disease: possible variant of Waardenburg syndrome. J Pediatr. 1981 Sep;99(3):432–435. doi: 10.1016/s0022-3476(81)80339-3. [DOI] [PubMed] [Google Scholar]
  42. Sparkes R. S., Sparkes M. C., Kalina R. E., Pagon R. A., Salk D. J., Disteche C. M. Separation of retinoblastoma and esterase D loci in a patient with sporadic retinoblastoma and del(13)(q14.1q22.3). Hum Genet. 1984;68(3):258–259. doi: 10.1007/BF00418397. [DOI] [PubMed] [Google Scholar]
  43. Spritz R. A., Giebel L. B., Holmes S. A. Dominant negative and loss of function mutations of the c-kit (mast/stem cell growth factor receptor) proto-oncogene in human piebaldism. Am J Hum Genet. 1992 Feb;50(2):261–269. [PMC free article] [PubMed] [Google Scholar]
  44. Tachibana M., Perez-Jurado L. A., Nakayama A., Hodgkinson C. A., Li X., Schneider M., Miki T., Fex J., Francke U., Arnheiter H. Cloning of MITF, the human homolog of the mouse microphthalmia gene and assignment to chromosome 3p14.1-p12.3. Hum Mol Genet. 1994 Apr;3(4):553–557. doi: 10.1093/hmg/3.4.553. [DOI] [PubMed] [Google Scholar]
  45. Tassabehji M., Newton V. E., Read A. P. Waardenburg syndrome type 2 caused by mutations in the human microphthalmia (MITF) gene. Nat Genet. 1994 Nov;8(3):251–255. doi: 10.1038/ng1194-251. [DOI] [PubMed] [Google Scholar]
  46. Tassabehji M., Read A. P., Newton V. E., Harris R., Balling R., Gruss P., Strachan T. Waardenburg's syndrome patients have mutations in the human homologue of the Pax-3 paired box gene. Nature. 1992 Feb 13;355(6361):635–636. doi: 10.1038/355635a0. [DOI] [PubMed] [Google Scholar]
  47. WAARDENBURG P. J. A new syndrome combining developmental anomalies of the eyelids, eyebrows and nose root with pigmentary defects of the iris and head hair and with congenital deafness. Am J Hum Genet. 1951 Sep;3(3):195–253. [PMC free article] [PubMed] [Google Scholar]
  48. White A., Tomfohrde J., Stewart E., Barnes R., Le Paslier D., Weissenbach J., Cavalli-Sforza L., Farrer L., Bowcock A. A 4.5-megabase yeast artificial chromosome contig from human chromosome 13q14.3 ordering 9 polymorphic microsatellites (22 sequence-tagged sites) tightly linked to the Wilson disease locus. Proc Natl Acad Sci U S A. 1993 Nov 1;90(21):10105–10109. doi: 10.1073/pnas.90.21.10105. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Journal of Medical Genetics are provided here courtesy of BMJ Publishing Group

RESOURCES