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CXorf6 is a causative gene for hypospadias

A Corrigendum to this article was published on 01 January 2007

This article has been updated


46,XY disorders of sex development (DSD) refer to a wide range of abnormal genitalia, including hypospadias, which affects 0.5% of male newborns. We identified three different nonsense mutations of CXorf6 in individuals with hypospadias and found that its mouse homolog was specifically expressed in fetal Sertoli and Leydig cells around the critical period for sex development. These data imply that CXorf6 is a causative gene for hypospadias.

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Figure 1: Molecular and clinical findings.
Figure 2: In situ hybridization analysis of the mouse CXorf6 homolog.

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  • 07 December 2006

    Agneta Nordenskjöld is in the Department of Molecular Medicine and Surgery, Karolinska University Hospital, Stockholm, Sweden. This error has been corrected in the HTML and PDF versions of the article.


  1. Laporte, J. et al. Hum. Mol. Genet. 6, 1505–1511 (1997).

    Article  CAS  Google Scholar 

  2. Biancalana, V. et al. Hum. Genet. 112, 135–142 (2003).

    PubMed  Google Scholar 

  3. Hu, L.J. et al. Hum. Mol. Genet. 5, 139–143 (1996).

    Article  CAS  Google Scholar 

  4. Bartsch, O., Kress, W., Wagner, A. & Seemanova, E. Cytogenet. Cell Genet. 85, 310–314 (1999).

    Article  CAS  Google Scholar 

  5. Laporte, J. et al. Genomics 41, 458–462 (1997).

    Article  CAS  Google Scholar 

  6. Winter, J.S.D. et al. J. Clin. Endocrinol. Metab. 42, 679–686 (1976).

    Article  CAS  Google Scholar 

  7. Hentze, M.W. & Kulozik, A.E. Cell 96, 307–310 (1999).

    Article  CAS  Google Scholar 

  8. Tsai, T.C. et al. Neuromuscul. Disord. 15, 245–252 (2005).

    Article  Google Scholar 

  9. Grumbach, M.M., Hughes, I.A. & Conte, F.A. Disorders of Sex Differentiation: Williams Textbook of Endocrinology 10th edn. 842–1002 (Saunders, Philadelphia, 2002).

  10. Nomura, M. et al. J. Biochem. 124, 217–224 (1998).

    Article  CAS  Google Scholar 

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We thank M. Kaji, T. Nagai, I. Sasagawa, K. Ueoka, K. Aoki, W. Kress, O. Bartsch, V. Biancalana, L. Van Maldergem and A. Nordenskjöld for providing us with blood samples from patients; T. Chen, Q. Li, and Y. Shen for participating in the mutation screening; K. Homma for urine steroid profile analysis and F. Kato for technical assistance. This work was supported by a grant for Child Health and Development from the Ministry of Health, Labor and Welfare of Japan (17C-2); by a Grant-in-Aid for Scientific Research on Priority Areas from the Ministry of Education, Science, Sports and Culture of Japan (16086215 and 16590218) and by the Institut National de la Santé et de la Recherche Médicale, the Centre National de la Recherche Scientifique and the College de France.

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Mutation analysis was performed by M.F., Y.W., G.C., C.K. and A.B.-B.; human cDNA screening and RT-PCR by M.F.; mouse expression analysis by K.M., G.Y. and K.M. and phenotype assessment by I.N., T.H., J.L. and T.O. The study was designed and coordinated by J.L. and T.O., and the paper was written by T.O.

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Correspondence to Tsutomu Ogata.

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The authors declare no competing financial interests.

Supplementary information

Supplementary Fig. 1

PCR-based screening for CXorf6 using human cDNA. (PDF 491 kb)

Supplementary Table 1

Patients examined in the present study with 46,XY disorders of sex development. (PDF 35 kb)

Supplementary Table 2

Primers used in this study. (PDF 21 kb)

Supplementary Table 3

Summary of the four Japanese individuals with a nonsense mutation in CXorf6. (PDF 64 kb)

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Fukami, M., Wada, Y., Miyabayashi, K. et al. CXorf6 is a causative gene for hypospadias. Nat Genet 38, 1369–1371 (2006).

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