Search tips
Search criteria 


Logo of jmedgeneJournal of Medical GeneticsVisit this articleSubmit a manuscriptReceive email alertsContact usBMJ
J Med Genet. 1990 October; 27(10): 618–626.
PMCID: PMC1017240

Mouse and hamster mutants as models for Waardenburg syndromes in humans.


Four different Waardenburg syndromes have been defined based upon observed phenotypes. These syndromes are responsible for approximately 2% of subjects with profound congenital hearing loss. At present, Waardenburg syndromes have not been mapped to particular human chromosomes. One or more of the mouse mutant alleles, Ph (patch), s (piebald), Sp (splotch), and Mior (microphthalmia-Oak Ridge) and the hamster mutation Wh (anophthalmic white) may be homologous to mutations causing Waardenburg syndromes. In heterozygotes, phenotypic effects of these four mouse mutations and the hamster mutation are similar to the phenotypes produced by different Waardenburg syndrome mutations. The chromosomal locations and syntenic relationships associated with three of the four mouse mutant genes have been used to predict human chromosomal locations for Waardenburg syndromes: (1) on chromosome 2q near FN1 (fibronectin 1), (2) on chromosome 3p near the proto-oncogene RAF1 or 3q near RHO (rhodopsin), and (3) on chromosome 4p near the proto-oncogene KIT. Waardenburg syndromes show extensive intrafamilial phenotypic variability. Results of our studies with the hamster mutation Wh suggest that this variability may be explained in part by modifier genes segregating within families.

Full text

Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (1.9M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.

Images in this article

Click on the image to see a larger version.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • WAARDENBURG PJ. 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. [PubMed]
  • Wang L, Karmody CS, Pashayan H. Waardenburg's syndrome: variations in expressivity. Otolaryngol Head Neck Surg. 1981 Jul-Aug;89(4):666–670. [PubMed]
  • Preus M, Linstrom C, Polomeno RC, Milot J. Waardenburg syndrome--penetrance of major signs. Am J Med Genet. 1983 Jul;15(3):383–388. [PubMed]
  • Arias S. Diagnosis and penetrance of dystopia canthorum in Waardenburg syndrome type I (WS1) Am J Med Genet. 1984 Apr;17(4):863–867. [PubMed]
  • Arias S. Genetic heterogeneity in the Waardenburg syndrome. Birth Defects Orig Artic Ser. 1971 Mar;07(4):87–101. [PubMed]
  • Pantke OA, Cohen MM., Jr The Waardenburg syndrome. Birth Defects Orig Artic Ser. 1971 Jun;7(7):147–152. [PubMed]
  • DIGEORGE AM, OLMSTED RW, HARLEY RD. 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. [PubMed]
  • Goldberg MF. Waardenburg's syndrome with fundus and other anomalies. Arch Ophthalmol. 1966 Dec;76(6):797–810. [PubMed]
  • Delleman JW, Hageman MJ. Ophthalmological findings in 34 patients with Waardenburg syndrome. J Pediatr Ophthalmol Strabismus. 1978 Nov-Dec;15(6):341–345. [PubMed]
  • Hageman MJ, Delleman JW. Heterogeneity in Waardenburg syndrome. Am J Hum Genet. 1977 Sep;29(5):468–485. [PubMed]
  • Arias S. Waardenburg syndrome--two distinct types. Am J Med Genet. 1980;6(1):99–100. [PubMed]
  • Bard LA. Heterogeneity in Waardenburg's syndrome. Report of a family with ocular albinism. Arch Ophthalmol. 1978 Jul;96(7):1193–1198. [PubMed]
  • 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. [PubMed]
  • Goodman RM, Lewithal I, Solomon A, Klein D. Upper limb involvement in the Klein-Waardenburg syndrome. Am J Med Genet. 1982 Apr;11(4):425–433. [PubMed]
  • Omenn GS, McKusick VA. The association of Waardenburg syndrome and Hirschsprung megacolon. Am J Med Genet. 1979;3(3):217–223. [PubMed]
  • Shah KN, Dalal SJ, Desai MP, Sheth PN, Joshi NC, Ambani LM. White forelock, pigmentary disorder of irides, and long segment Hirschsprung disease: possible variant of Waardenburg syndrome. J Pediatr. 1981 Sep;99(3):432–435. [PubMed]
  • Ambani LM. Waardenburg and Hirschsprung syndromes. J Pediatr. 1983 May;102(5):802–802. [PubMed]
  • Meire F, Standaert L, De Laey JJ, Zeng LH. Waardenburg syndrome, Hirschsprung megacolon, and Marcus Gunn ptosis. Am J Med Genet. 1987 Jul;27(3):683–686. [PubMed]
  • Spence MA, Tsui LC. Report of the committee on the genetic constitution of chromosomes 7, 8 and 9. Cytogenet Cell Genet. 1987;46(1-4):170–187. [PubMed]
  • Cook PJ, Robson EB, Buckton KE, Slaughter CA, Gray JE, Blank CE, James FE, Ridler MA, Insley J, Hultén M. Segregation of ABO, AK1 and ACONs in families with abnormalities of chromosome 9. Ann Hum Genet. 1978 Jan;41(3):365–377. [PubMed]
  • Westerveld A, Jongsma AP, Meera Khan P, van Someren H, Bootsma D. Assignment of the AK1:Np:ABO linkage group to human chromosome 9. Proc Natl Acad Sci U S A. 1976 Mar;73(3):895–899. [PubMed]
  • Simpson JL, Falk CT, Morillo-Cucci G, Allen FH, Jr, German J. Analysis for possible linkage between the loci for the Waardenburg syndrome and various blood groups and serological traits. Humangenetik. 1974 Jun 26;23(1):45–50. [PubMed]
  • Arias S, Mota M, Yánez A, Bolivar M. Probable loose linkage between the ABO locus and Waardenburg syndrome type I. Humangenetik. 1975;27(2):145–149. [PubMed]
  • Arias S, Mota M. Current status of the ABO-Waardenburg syndrome type I linkage. Cytogenet Cell Genet. 1978;22(1-6):291–294. [PubMed]
  • MORTON NE. Further scoring types in sequential linkage tests, with a critical review of autosomal and partial sex linkage in man. Am J Hum Genet. 1957 Mar;9(1):55–75. [PubMed]
  • Watkins PC. Restriction fragment length polymorphism (RFLP): applications in human chromosome mapping and genetic disease research. Biotechniques. 1988 Apr;6(4):310–322. [PubMed]
  • 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. [PubMed]
  • Turleau C, Chavin-Colin F, de Grouchy J, Repessé G, Beauvais P. Familial t(X;2) (p223;q323) with partial trisomy 2q and male and female balanced carriers. Hum Genet. 1977 Jun 10;37(1):97–104. [PubMed]
  • Dennis NR, Neu RL, Bannerman RM. Duplication 2q33 leads to 2q37 due to paternal ins (12;2) translocation. Am J Med Genet. 1978;1(3):271–277. [PubMed]
  • Zankl M, Schwanitz G, Schmid P, Zankl H, Dockter G, Rodewald A, Zang KD, Grosse KP. Distal 2q duplication: report of two familial cases and an attempt to define a syndrome. Am J Med Genet. 1979;4(1):5–16. [PubMed]
  • Warter S, Lausecker C, Pennerath A. Etude chromosomique et clinique d'und fillette porteuse d'une deletion (2) (q34q36) Hum Genet. 1976 May 19;32(2):225–227. [PubMed]
  • Sánchez JM, Pantano AM. A case of deletion 2q35----qter and a peculiar phenotype. J Med Genet. 1984 Apr;21(2):147–149. [PMC free article] [PubMed]
  • Glass IA, Swindlehurst CA, Aitken DA, 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. [PMC free article] [PubMed]
  • Benson K, Gordon M, Wassman ER, Tsi C. Interstitial deletion of the long arm of chromosome 2 in a malformed infant with karyotype 46,XX,del(2)(q31q33). Am J Med Genet. 1986 Nov;25(3):405–411. [PubMed]
  • Young RS, Shapiro SD, Hansen KL, Hine LK, Rainosek DE, Guerra FA. Deletion 2q: two new cases with karyotypes 46,XY,del(2)(q31q33) and 46,XX,del(2)(q36). J Med Genet. 1983 Jun;20(3):199–202. [PMC free article] [PubMed]
  • Buchanan PD, Rhodes RL, Stevenson CE., Jr Interstitial deletion 2q31 leads to q33. Am J Med Genet. 1983 May;15(1):121–126. [PubMed]
  • Al-Awadi SA, Farag TI, Naguib K, Teebi A, Cuschieri A, Al-Othman S, Sundareshan TS. Interstitial deletion of the long arm of chromosome 2: del(2)(q31q33). J Med Genet. 1983 Dec;20(6):464–465. [PMC free article] [PubMed]
  • Franceschini P, Cirillo Silengo M, Davi G, Bianco R, Biagioli M. Interstitial deletion of the long arm of chromosome 2 (q31q33) in a girl with multiple anomalies and mental retardation. Hum Genet. 1983;64(1):98–98. [PubMed]
  • Taysi K, Dengler DR, Jones LA, Heersma JR. Interstitial deletion of the long arm of chromosome 2: case report and review of literature. Ann Genet. 1981;24(4):245–247. [PubMed]
  • Pai GS, Rogers JF, Sommer A. Identical multiple congenital anomalies/mental retardation (MCA/MR) syndrome due to del(2)(q32) in two sisters with intrachromosomal insertional translocation in their father. Am J Med Genet. 1983 Jan;14(1):189–195. [PubMed]
  • WILSON TG, KANE F. Congenital deafness in white cats. Acta Otolaryngol. 1959 May-Aug;50(3-4):269–277. [PubMed]
  • Bosher SK, Hallpike CS. Observations on the histogenesis of the inner ear degeneration of the deaf white cat and its possible relationship to the aetiology of certain unexplained varieties of human congenital deafness. J Laryngol Otol. 1966 Mar;80(3):222–235. [PubMed]
  • Brown KS, Bergsma DR, Barrow MV. Animal models of pigment and hearing abnormalities in man. Birth Defects Orig Artic Ser. 1971 Mar;07(4):102–109. [PubMed]
  • Hilding DA, Sugiura A, Nakai Y. Deaf white mink: electron microscopic study of the inner ear. Ann Otol Rhinol Laryngol. 1967 Aug;76(3):647–663. [PubMed]
  • Asher JH., Jr Concerning the primary defect leading to the pleiotropic effects caused by anophthalmic white (Wh) in the Syrian hamster Mesocricetus auratus. J Exp Zool. 1981 Aug;217(2):159–169. [PubMed]
  • Nadeau JH. Maps of linkage and synteny homologies between mouse and man. Trends Genet. 1989 Mar;5(3):82–86. [PubMed]
  • Cotzias GC, Tang LC, Miller ST, Sladic-Simic D, Hurley LS. A mutation influencing the transportation of manganese, L-dopa, and L-tryptophan. Science. 1972 Apr 28;176(4033):410–412. [PubMed]
  • Novak EK, Swank RT. Lysosomal dysfunctions associated with mutations at mouse pigment genes. Genetics. 1979 May;92(1):189–204. [PubMed]
  • Mayer TC, Green MC. An experimental analysis of the pigment defect caused by mutations at the W and S1 loci in mice. Dev Biol. 1968 Jul;18(1):62–75. [PubMed]
  • MINTZ B, RUSSELL ES. Gene-induced embryological modifications of primordial germ cells in the mouse. J Exp Zool. 1957 Mar;134(2):207–237. [PubMed]
  • Geissler EN, Ryan MA, Housman DE. The dominant-white spotting (W) locus of the mouse encodes the c-kit proto-oncogene. Cell. 1988 Oct 7;55(1):185–192. [PubMed]
  • DEOL MS. THE ORIGIN OF THE ABNORMALITIES OF THE INNER EAR IN DREHER MICE. J Embryol Exp Morphol. 1964 Dec;12:727–733. [PubMed]
  • Lyon MF, Meredith R. Muted, a new mutant affecting coat colour and otoliths of the mouse, and its position in linkage group XIV. Genet Res. 1969 Oct;14(2):163–166. [PubMed]
  • O'Brien SJ, Seuánez HN, Womack JE. Mammalian genome organization: an evolutionary view. Annu Rev Genet. 1988;22:323–351. [PubMed]
  • Searle AG, Truslove GM. A gene triplet in the mouse. Genet Res. 1970 Apr;15(2):227–235. [PubMed]
  • Jeffreys AJ, Wilson V, Kelly R, Taylor BA, Bulfield G. Mouse DNA 'fingerprints': analysis of chromosome localization and germ-line stability of hypervariable loci in recombinant inbred strains. Nucleic Acids Res. 1987 Apr 10;15(7):2823–2836. [PMC free article] [PubMed]
  • Truslove GM. A new allele at the patch locus in the mouse. Genet Res. 1977 Apr;29(2):183–186. [PubMed]
  • Yarden Y, Kuang WJ, Yang-Feng T, Coussens L, Munemitsu S, Dull TJ, Chen E, Schlessinger J, Francke U, Ullrich A. Human proto-oncogene c-kit: a new cell surface receptor tyrosine kinase for an unidentified ligand. EMBO J. 1987 Nov;6(11):3341–3351. [PubMed]
  • BIELSCHOWSKY M, SCHOFIELD GC. Studies on megacolon in piebald mice. Aust J Exp Biol Med Sci. 1962 Oct;40:395–403. [PubMed]
  • Addison RF, Zinck ME. The metabolism of some DDT-type compounds by brook trout (Salvelinus fontinalis). Environ Qual Saf Suppl. 1975;3:500–506. [PubMed]
  • Lalley PA, Davison MT, Graves JA, O'Brien SJ, Womack JE, Roderick TH, Creau-Goldberg N, Hillyard AL, Doolittle DP, Rogers JA. Report of the committee on comparative mapping. Cytogenet Cell Genet. 1989;51(1-4):503–532. [PubMed]
  • Packer SO. The eye and skeletal effects of two mutant alleles at the microphthalmia locus of Mus musculus. J Exp Zool. 1967 Jun;165(1):21–45. [PubMed]
  • Deol MS. The relationship between abnormalities of pigmentation and of the inner ear. Proc R Soc Lond B Biol Sci. 1970 Apr 7;175(1039):201–217. [PubMed]
  • West JD, Fisher G, Loutit JF, Marshall MJ, Nisbet NW, Perry VH. A new allele of microphthalmia induced in the mouse: microphthalmia--defective iris (midi). Genet Res. 1985 Dec;46(3):309–324. [PubMed]
  • Deol MS. The neural crest and the acoustic ganglion. J Embryol Exp Morphol. 1967 Jun;17(3):533–541. [PubMed]
  • Bonner T, O'Brien SJ, Nash WG, Rapp UR, Morton CC, Leder P. The human homologs of the raf (mil) oncogene are located on human chromosomes 3 and 4. Science. 1984 Jan 6;223(4631):71–74. [PubMed]
  • Kozak C, Gunnell MA, Rapp UR. A new oncogene, c-raf, is located on mouse chromosome 6. J Virol. 1984 Jan;49(1):297–299. [PMC free article] [PubMed]
  • Sparkes RS, Mohandas T, Newman SL, Heinzmann C, Kaufman D, Zollman S, Leveille PJ, Tobin AJ, McGinnis JF. Assignment of the rhodopsin gene to human chromosome 3. Invest Ophthalmol Vis Sci. 1986 Jul;27(7):1170–1172. [PubMed]
  • Jacobs KW. 16 PF correlates of sensation-seeking: an expansion and validation. Psychol Rep. 1975 Dec;37(3 Pt 2):1215–1218. [PubMed]
  • Pratt BM. Site of gene action of the white allele (Miwh) of the microphthalmia locus: a dermal-epidermal recombination study. J Exp Zool. 1982 Mar 1;220(1):93–101. [PubMed]
  • James SC, Hooper G, Asher JH., Jr Effects of the gene Wh on reproduction in the Syrian hamster, Mesocricetus auratus. J Exp Zool. 1980 Dec;214(3):261–275. [PubMed]
  • James SC, Asher JH., Jr A histological examination of the pars distalis from the Syrian hamster mutant Anophthalmic white (Wh). J Exp Zool. 1981 Dec;218(3):335–350. [PubMed]
  • Asher JH, Jr, James SC. The primary ultrastructural defect caused by anophthalmic white (Wh) in the Syrian hamster. Proc Natl Acad Sci U S A. 1982 Jul;79(14):4371–4375. [PubMed]
  • Hagen SC, Asher JH., Jr Effects of pinealectomy on reproduction in the Syrian hamster mutant anophthalmic white (Wh). Am J Anat. 1983 Aug;167(4):523–538. [PubMed]

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