Journal of Pediatric Surgery
Volume 44, Issue 10 , Pages 1892-1898 , October 2009

MNX1 (HLXB9) mutations in Currarino patients

  • Maria-Mercè Garcia-Barceló

      Affiliations

    • Department of Surgery, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China
    • Center for Reproduction, Development and Growth, The University of Hong Kong, Hong Kong SAR, China
    • ,
  • Vincent Chi-Hang Lui

      Affiliations

    • Department of Surgery, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China
    • Center for Reproduction, Development and Growth, The University of Hong Kong, Hong Kong SAR, China
    • ,
  • Man-ting So

      Affiliations

    • Department of Surgery, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China
    • ,
  • Xiaoping Miao

      Affiliations

    • Department of Surgery, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China
    • Current affiliation: Department of Surgery, Shenzhen Children's Hospital, Shenzhen, China.
    • ,
  • Thomas Yuk-yu Leon

      Affiliations

    • Department of Surgery, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China
    • ,
  • Zhen-wei Yuan

      Affiliations

    • Department of Pediatric Surgery, Shengjing Hospital, China Medical University, Shenyang, China
    • ,
  • Elly Sau-wai Ngan

      Affiliations

    • Department of Surgery, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China
    • Center for Reproduction, Development and Growth, The University of Hong Kong, Hong Kong SAR, China
    • ,
  • Toufique Ehsan

      Affiliations

    • Department of Surgery, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China
    • Current affiliation: Department of Pediatric Surgery, Holy Family Red Crescent Medical College Hospital, Dhaka, Bangladesh.
    • ,
  • Patrick Ho-yu Chung

      Affiliations

    • Department of Surgery, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China
    • ,
  • Pek-lan Khong

      Affiliations

    • Department of Pediatric Surgery, Shengjing Hospital, China Medical University, Shenyang, China
    • Department of Radiology, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong SAR, China
    • ,
  • Kenneth Kak-yuen Wong

      Affiliations

    • Department of Surgery, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China
    • Corresponding Author InformationCorresponding authors. Division of Pediatric Surgery, Department of Surgery, Queen Mary Hospital, Li Ka Shing Faculty of Medicine of the University of Hong Kong, Hong Kong. Tel.: +852 28554850; fax: +852 28173155.
    • ,
  • Paul Kwong-hang Tam

      Affiliations

    • Department of Surgery, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China
    • Center for Reproduction, Development and Growth, The University of Hong Kong, Hong Kong SAR, China
    • Corresponding Author InformationCorresponding authors. Division of Pediatric Surgery, Department of Surgery, Queen Mary Hospital, Li Ka Shing Faculty of Medicine of the University of Hong Kong, Hong Kong. Tel.: +852 28554850; fax: +852 28173155.

Received 14 November 2008 ,Revised 7 February 2009 ,Accepted 24 March 2009.

References 

  1. Currarino G, Coln D, Votteler T. Triad of anorectal, sacral, and presacral anomalies. AJR Am J Roentgenol. 1981;137:395–398
  2. Scherer S, Martucciello G, Belloni E, et al. HLXB9 and sacral agenesis and the Currarino syndrome. In:  Epstein CJ,  Erickson RP,  Wynshaw-Boris A editor. Inborn errors of development, the molecular basis of clinical disorders of morphogenesis. New York: Oxford University Press; 2004;p. 578–587
  3. Lynch SA, Wang Y, Strachan T, et al. Autosomal dominant sacral agenesis: Currarino syndrome. J Med Genet. 2000;37:561–566
  4. Hagan DM, Ross AJ, Strachan T, et al. Mutation analysis and embryonic expression of the HLXB9 Currarino syndrome gene. Am J Hum Genet. 2000;66:1504–1515
  5. Belloni E, Martucciello G, Verderio D, et al. Involvement of the HLXB9 homeobox gene in Currarino syndrome. Am J Hum Genet. 2000;66:312–319
  6. Lynch SA, Bond PM, Copp AJ, et al. A gene for autosomal dominant sacral agenesis maps to the holoprosencephaly region at 7q36. Nat Genet. 1995;11:93–95
  7. Ross AJ, Ruiz-Perez V, Wang Y, et al. A homeobox gene, HLXB9, is the major locus for dominantly inherited sacral agenesis. Nat Genet. 1998;20:358–361
  8. Harrison KA, Druey KM, Deguchi Y, et al. A novel human homeobox gene distantly related to proboscipedia is expressed in lymphoid and pancreatic tissues. J Biol Chem. 1994;269:19968–19975
  9. Li H, Arber S, Jessell TM, et al. Selective agenesis of the dorsal pancreas in mice lacking homeobox gene Hlxb9. Nat Genet. 1999;23:67–70
  10. Thaler J, Harrison K, Sharma K, et al. Active suppression of interneuron programs within developing motor neurons revealed by analysis of homeodomain factor HB9. Neuron. 1999;23:675–687
  11. Arber S, Han B, Mendelsohn M, et al. Requirement for the homeobox gene Hb9 in the consolidation of motor neuron identity. Neuron. 1999;23:659–674
  12. Amiel J, Trochet D, Clement-Ziza M, et al. Polyalanine expansions in human. Hum. Mol. Genet. 2004;13(Spec No 2):R235–R243
  13. Lavoie H, Debeane F, Trinh QD, et al. Polymorphism, shared functions and convergent evolution of genes with sequences coding for polyalanine domains. Hum Mol Genet. 2003;12:2967–2979
  14. Albrecht AN, Kornak U, Boddrich A, et al. A molecular pathogenesis for transcription factor associated poly-alanine tract expansions. Hum Mol Genet. 2004;13:2351–2359
  15. Kochling J, Karbasiyan M, Reis A. Spectrum of mutations and genotype-phenotype analysis in Currarino syndrome. Eur J Hum Genet. 2001;9:599–605
  16. Garcia-Barcelo M, So MT, Lau DK, et al. Population differences in the polyalanine domain and 6 new mutations in HLXB9 in patients with Currarino syndrome. Clin Chem. 2006;52:46–52
  17. Amornfa J, Taecholarn C, Khaoroptham S. Currarino syndrome: report of two cases and review of the literature. J Med Assoc Thai. 2005;88:1697–1702
  18. Kilickesmez O, Gol IH, Uzun M, et al. Complete familial Currarino triad in association with Hirschsprung's disease: magnetic resonance imaging features and the spectrum of anorectal malformations. Acta Radiol. 2006;47:422–426
  19. Martucciello G, Torre M, Belloni E, et al. Currarino syndrome: proposal of a diagnostic and therapeutic protocol. J Pediatr Surg. 2004;39:1305–1311
  20. Baltogiannis N, Mavridis G, Soutis M, et al. Currarino triad associated with Hirschsprung's disease. J Pediatr Surg. 2003;38:1086–1089
  21. Volk A, Karbasiyan M, Semmler A, et al. Adult index patient with Currarino syndrome due to a novel HLXB9 mutation, c.336dupG (p.P113fsX224), presenting with Hirschsprung's disease, cephalgia, and lumbodynia. Birth Defects Res A Clin Mol Teratol. 2007;79:249–251
  22. Piper DE, Batchelor AH, Chang CP, et al. Structure of a HoxB1-Pbx1 heterodimer bound to DNA: role of the hexapeptide and a fourth homeodomain helix in complex formation. Cell. 1999;96:587–597
  23. Ippel H, Larsson G, Behravan G, et al. The solution structure of the homeodomain of the rat insulin-gene enhancer protein isl-1. Comparison with other homeodomains. J Mol Biol. 1999;288:689–703
  24. D'Elia AV, Tell G, Paron I, et al. Missense mutations of human homeoboxes: a review. Hum Mutat. 2001;18:361–374
  25. Swain PK, Chen S, Wang QL, et al. Mutations in the cone-rod homeobox gene are associated with the cone-rod dystrophy photoreceptor degeneration. Neuron. 1997;19:1329–1336
  26. Sohocki MM, Sullivan LS, Mintz-Hittner HA, et al. A range of clinical phenotypes associated with mutations in CRX, a photoreceptor transcription-factor gene. Am J Hum Genet. 1998;63:1307–1315
  27. Chi YI. Homeodomain revisited: a lesson from disease-causing mutations. Hum Genet. 2005;116:433–444
  28. Clarke ND, Kissinger CR, Desjarlais J, et al. Structural studies of the engrailed homeodomain. Protein Sci. 1994;3:1779–1787
  29. Derossi D, Joliot AH, Chassaing G, et al. The third helix of the Antennapedia homeodomain translocates through biological membranes. J Biol Chem. 1994;269:10444–10450
  30. Hombria JC, Lovegrove B. Beyond homeosis-HOX function in morphogenesis and organogenesis. Differentiation. 2003;71:461–476

 Drs. Garcia-Barceló and Lui contributed equally to the study.

PII: S0022-3468(09)00311-X

doi: 10.1016/j.jpedsurg.2009.03.039

Journal of Pediatric Surgery
Volume 44, Issue 10 , Pages 1892-1898 , October 2009

Article Tools

* Image Usage & Resolution