Fertility and Sterility
Volume 94, Issue 4 , Pages 1235-1238 , September 2010

A novel mutation of HOXA13 in a family with hand-foot-genital syndrome and the role of polyalanine expansions in the spectrum of Müllerian fusion anomalies

  • Elisa M. Jorgensen, B.S.

      Affiliations

    • Division of Reproductive Endocrinology and Infertility, Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, New Haven, Connecticut
    • ,
  • Jane I. Ruman, M.D.

      Affiliations

    • Department of Obstetrics, Gynecology and Reproductive Science, Mount Sinai School of Medicine, New York, New York
    • ,
  • Leo Doherty, M.D.

      Affiliations

    • Division of Reproductive Endocrinology and Infertility, Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, New Haven, Connecticut
    • ,
  • Hugh S. Taylor, M.D.

      Affiliations

    • Division of Reproductive Endocrinology and Infertility, Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, New Haven, Connecticut
    • Corresponding Author InformationReprint requests: Hugh Taylor, M.D., Division of Reproductive Endocrinology and Infertility, Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06510 (FAX: 203-785-7819).

Received 17 April 2009 ,Revised 26 May 2009 ,Accepted 27 May 2009.

References 

  1. Stern AM, Gall JC, Perry BL, Stimson CW, Weitkamp LR, Poznanski AK. The hand-food-uterus syndrome: a new hereditary disorder characterized by hand and foot dysplasia, dermatoglyphic abnormalities, and partial duplication of the female genital tract. J Pediatr. 1970;77:109–116
  2. Poznanski AK, Kuhns LR, Lapides J, Stern AM. A new family with the hand-foot-genital syndrome—a wider spectrum of the hamd-foot-uterus syndrome. Birth Defects Orig Artic Ser. 1975;11:127–135
  3. Giedion A, Prader A. Hand-foot-uterus (HFU) syndrome with hypospadias: the hand-foot-genital (HFG) syndrome. Pediatr Radiol. 1976;4:96–102
  4. Verp MS, Simpson JL, Elias S, Carson SA, Sarto GE, Feingold M. Heritable aspects of uterine anomalies. I. Three familial aggregates with Mullerian fusion anomalies. Fertil Steril. 1983;40:80–85
  5. Mortlock DP, Innis JW. Mutation of HOXA13 in hand-foot-genital syndrome. Nat Genet. 1997;15:179–180
  6. Du H, Taylor HS. Molecular regulation of mullerian development by Hox genes. Ann N Y Acad Sci. 2004;1034:152–165
  7. Utsch B, Becker K, Brock D, Lentze MJ, Bidlingmaier F, Ludwig M. A novel stable polyalanine [poly(A)] expansion in the HOXA13 gene associated with hand-foot-genital syndrome: proper function of poly(A)-harbouring transcription factors depends on a critical repeat length?. Hum Genet. 2002;110:488–494
  8. Frisen L, Lagerstedt K, Tapper-Persson M, Kockum I, Nordenskjold A. A novel duplication in the HOXA13 gene in a family with atypical hand-foot-genital syndrome. J Med Genet. 2003;40:e49
  9. Goodman FR, Bacchelli C, Brady AF, Brueton LA, Fryns JP, Mortlock DP, et al. Novel HOXA13 mutations and the phenotypic spectrum of hand-foot-genital syndrome. Am J Hum Genet. 2000;67:197–202
  10. Innis JW, Mortlock D, Chen Z, Ludwig M, Williams ME, Williams TM, et al. Polyalanine expansion in HOXA13: three new affected families and the molecular consequences in a mouse model. Hum Mol Genet. 2004;13:2841–2851
  11. Debeer P, Bacchelli C, Scambler PJ, De Smet L, Fryns JP, Goodman FR. Severe digital abnormalities in a patient heterozygous for both a novel missense mutation in HOXD13 and a polyalanine tract expansion in HOXA13. J Med Genet. 2002;39:852–856
  12. Utsch B, McCabe CD, Galbraith K, Gonzalez R, Born M, Dotsch J, et al. Molecular characterization of HOXA13 polyalanine expansion proteins in hand-foot-genital syndrome. Am J Med Genet A. 2007;143A:3161–3168
  13. Albrecht AN, Kornak U, Boddrich A, Suring K, Robinson PN, Stiege AC, et al. A molecular pathogenesis for transcription factor associated poly-alanine tract expansions. Hum Mol Genet. 2004;13:2351–2359
  14. Poncelet C, Aissaoui F. Uterine malformations and reproduction. Gynecol Obstet Fertil. 2007;35:821–825
  15. Goodman FR. Limb malformations and the human HOX genes. Am J Med Genet. 2002;112:256–265
  16. Taylor HS. Transcriptional regulation of implantation by HOX genes. Rev Endocrinol Metab Disord. 2002;3:127–132
  17. Daftary GS, Taylor HS. Endocrine regulation of HOX genes. Endocrinol Rev. 2006;27:331–355
  18. Taylor E, Gomel V. The uterus and fertility. Fertil Steril. 2008;89:1–16

 E.M.J. has nothing to disclose. J.I.R. has nothing to disclose. L.D. has nothing to disclose. H.S.T. has nothing to disclose.

 Supported by National Institute of Environmental Health Sciences grants ES010610 and U54 HD052668.

PII: S0015-0282(09)01205-9

doi: 10.1016/j.fertnstert.2009.05.057

Fertility and Sterility
Volume 94, Issue 4 , Pages 1235-1238 , September 2010

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