Skip to main content
PMC home page
American Journal of Human Genetics logoLink to American Journal of Human Genetics
. 1991 Jan;48(1):43–52.

Waardenburg syndrome (WS): the analysis of a single family with a WS1 mutation showing linkage to RFLP markers on human chromosome 2q.

J H Asher Jr 1, R Morell 1, T B Friedman 1
PMCID: PMC1682754  PMID: 1670751

Abstract

Waardenburg syndrome type I (WS1; MIM 19350) is caused by a pleiotropic, autosomal dominant mutation with variable penetrance and expressivity. Of individuals with this mutation, 20%-25% are hearing impaired. A multilocus linkage analysis of RFLP data from a single WS1 family with 11 affected individuals indicates that the WS1 mutation in this family is linked to the following four marker loci located on the long arm of chromosome 2: ALPP (alkaline phosphatase, placental), FN1 (fibronectin 1), D2S3 (a unique-copy DNA segment), and COL6A3 (collagen VI, alpha 3). For the RFLP marker loci, a multilocus linkage analysis using MLINK produced a peak lod (Z) of 3.23 for the following linkage relationships and recombination fractions (theta i): (ALPP----.000----FN1)----.122----D2S3----.267----CO L6A3. A similar analysis produced a Z of 6.67 for the following linkage relationships and theta i values among the markers and WS1: (FN1----.000----WS1----.000----ALPP)----.123----D2S 3----.246----COL6A3. The data confirm the conclusion of Foy et al. that at least some WS1 mutations map to chromosome 2q.

Full text

PDF
47

Images in this article

46Figure 2
on p.46

Selected References

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

  1. Ahrendts H. Das Waardenburg-Syndrom, dargestellt an fünf Familien. Z Kinderheilkd. 1965 Sep 3;93(4):295–313. [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, Friedman T. B. Mouse and hamster mutants as models for Waardenburg syndromes in humans. J Med Genet. 1990 Oct;27(10):618–626. doi: 10.1136/jmg.27.10.618. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Barker D. F., Hostikka S. L., Zhou J., Chow L. T., Oliphant A. R., Gerken S. C., Gregory M. C., Skolnick M. H., Atkin C. L., Tryggvason K. Identification of mutations in the COL4A5 collagen gene in Alport syndrome. Science. 1990 Jun 8;248(4960):1224–1227. doi: 10.1126/science.2349482. [DOI] [PubMed] [Google Scholar]
  5. CALINIKOS J. Waardenburg's syndrome. J Laryngol Otol. 1963 Jan;77:59–62. doi: 10.1017/s0022215100060369. [DOI] [PubMed] [Google Scholar]
  6. Colombi M., Gardella R., Barlati S., Vaheri A. A frequent HaeIII RFLP of the human fibronectin gene. Nucleic Acids Res. 1987 Aug 25;15(16):6761–6761. doi: 10.1093/nar/15.16.6761. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. DIGEORGE A. M., OLMSTED R. W., HARLEY R. D. Waardenburg's syndrome. A syndrome of heterochromia of the irides, lateral displacement of the medial canthi and lacrimal puncta, congenital deafness, and other characteristic associated defects. J Pediatr. 1960 Nov;57:649–669. doi: 10.1016/s0022-3476(60)80159-x. [DOI] [PubMed] [Google Scholar]
  8. Delleman J. W., Hageman M. J. Ophthalmological findings in 34 patients with Waardenburg syndrome. J Pediatr Ophthalmol Strabismus. 1978 Nov-Dec;15(6):341–345. doi: 10.3928/0191-3913-19781101-03. [DOI] [PubMed] [Google Scholar]
  9. Donis-Keller H., Green P., Helms C., Cartinhour S., Weiffenbach B., Stephens K., Keith T. P., Bowden D. W., Smith D. R., Lander E. S. A genetic linkage map of the human genome. Cell. 1987 Oct 23;51(2):319–337. doi: 10.1016/0092-8674(87)90158-9. [DOI] [PubMed] [Google Scholar]
  10. Erickson C. A., Weston J. A. An SEM analysis of neural crest migration in the mouse. J Embryol Exp Morphol. 1983 Apr;74:97–118. [PubMed] [Google Scholar]
  11. Feinberg A. P., Vogelstein B. A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity. Anal Biochem. 1983 Jul 1;132(1):6–13. doi: 10.1016/0003-2697(83)90418-9. [DOI] [PubMed] [Google Scholar]
  12. 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]
  13. Francke U. Molecular genetics. A gene for Wilms tumour? Nature. 1990 Feb 22;343(6260):692–694. doi: 10.1038/343692a0. [DOI] [PubMed] [Google Scholar]
  14. Glass I. A., Swindlehurst C. A., Aitken D. A., McCrea W., Boyd E. Interstitial deletion of the long arm of chromosome 2 with normal levels of isocitrate dehydrogenase. J Med Genet. 1989 Feb;26(2):127–130. doi: 10.1136/jmg.26.2.127. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Goldberg M. F. Waardenburg's syndrome with fundus and other anomalies. Arch Ophthalmol. 1966 Dec;76(6):797–810. doi: 10.1001/archopht.1966.03850010799005. [DOI] [PubMed] [Google Scholar]
  16. Hageman M. J., Delleman J. W. Heterogeneity in Waardenburg syndrome. Am J Hum Genet. 1977 Sep;29(5):468–485. [PMC free article] [PubMed] [Google Scholar]
  17. 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]
  18. Kidd K. K., Bowcock A. M., Schmidtke J., Track R. K., Ricciuti F., Hutchings G., Bale A., Pearson P., Willard H. F., Gelernter J. Report of the DNA committee and catalogs of cloned and mapped genes and DNA polymorphisms. Cytogenet Cell Genet. 1989;51(1-4):622–947. doi: 10.1159/000132810. [DOI] [PubMed] [Google Scholar]
  19. Lange K., Spence M. A., Frank M. B. Application of the lod method to the detection of linkage between a quantitative trait and a qualitative marker: a simulation experiment. Am J Hum Genet. 1976 Mar;28(2):167–173. [PMC free article] [PubMed] [Google Scholar]
  20. 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]
  21. Lathrop G. M., Lalouel J. M., Julier C., Ott J. Strategies for multilocus linkage analysis in humans. Proc Natl Acad Sci U S A. 1984 Jun;81(11):3443–3446. doi: 10.1073/pnas.81.11.3443. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Le Douarin N. M., Smith J. Development of the peripheral nervous system from the neural crest. Annu Rev Cell Biol. 1988;4:375–404. doi: 10.1146/annurev.cb.04.110188.002111. [DOI] [PubMed] [Google Scholar]
  23. Litt M. A single-copy subclone, p1-25, from cosmid 1-5, defines a highly polymorphic RFLP on 2q35- greater than 37 [HGM8 no. D2S3]. Nucleic Acids Res. 1986 May 27;14(10):4378–4378. doi: 10.1093/nar/14.10.4378. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Noden D. M. Interactions and fates of avian craniofacial mesenchyme. Development. 1988;103 (Suppl):121–140. doi: 10.1242/dev.103.Supplement.121. [DOI] [PubMed] [Google Scholar]
  25. 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]
  26. PARTINGTON M. W. WAARDENBURG'S SYNDROME AND HETEROCHROMIA IRIDUM IN A DEAF SCHOOL POPULATION. Can Med Assoc J. 1964 Apr 25;90:1008–1017. [PMC free article] [PubMed] [Google Scholar]
  27. Pantke O. A., Cohen M. M., Jr The Waardenburg syndrome. Birth Defects Orig Artic Ser. 1971 Jun;7(7):147–152. [PubMed] [Google Scholar]
  28. Patel P. I., Franco B., Garcia C., Slaugenhaupt S. A., Nakamura Y., Ledbetter D. H., Chakravarti A., Lupski J. R. Genetic mapping of autosomal dominant Charcot-Marie-Tooth disease in a large French-Acadian kindred: identification of new linked markers on chromosome 17. Am J Hum Genet. 1990 Apr;46(4):801–809. [PMC free article] [PubMed] [Google Scholar]
  29. Preus M., Linstrom C., Polomeno R. C., Milot J. Waardenburg syndrome--penetrance of major signs. Am J Med Genet. 1983 Jul;15(3):383–388. doi: 10.1002/ajmg.1320150303. [DOI] [PubMed] [Google Scholar]
  30. Seizinger B. R., Rouleau G. A., Ozelius L. J., Lane A. H., Farmer G. E., Lamiell J. M., Haines J., Yuen J. W., Collins D., Majoor-Krakauer D. Von Hippel-Lindau disease maps to the region of chromosome 3 associated with renal cell carcinoma. Nature. 1988 Mar 17;332(6161):268–269. doi: 10.1038/332268a0. [DOI] [PubMed] [Google Scholar]
  31. 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]
  32. Wang L., Karmody C. S., Pashayan H. Waardenburg's syndrome: variations in expressivity. Otolaryngol Head Neck Surg. 1981 Jul-Aug;89(4):666–670. doi: 10.1177/019459988108900428. [DOI] [PubMed] [Google Scholar]
  33. Weaver E. J., Chu M. L., Knowlton R. G. A BglI polymorphism in the type VI (alpha 3) procollagen gene [COL6A3]. Nucleic Acids Res. 1988 Dec 9;16(23):11386–11386. doi: 10.1093/nar/16.23.11386. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Weil D., Mattei M. G., Passage E., N'Guyen V. C., Pribula-Conway D., Mann K., Deutzmann R., Timpl R., Chu M. L. Cloning and chromosomal localization of human genes encoding the three chains of type VI collagen. Am J Hum Genet. 1988 Mar;42(3):435–445. [PMC free article] [PubMed] [Google Scholar]

Articles from American Journal of Human Genetics are provided here courtesy of American Society of Human Genetics

RESOURCES