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CXorf6 is a causative gene for hypospadias

Nature Genetics volume 38, pages 1369–1371 (2006)Cite this article

A Corrigendum to this article was published on 01 January 2007

This article has been updated

Abstract

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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Change history

  • 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.

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Acknowledgements

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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Author notes

  1. Maki Fukami and Yuka Wada: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Endocrinology and Metabolism, National Research Institute for Child Health and Development, Tokyo, 157-8535, Japan

    Maki Fukami, Yuka Wada & Tsutomu Ogata

  2. Division for Sex Differentiation, National Institute for Basic Biology, Okazaki, 444-8787, Japan

    Kanako Miyabayashi & Ken-ichirou Morohashi

  3. Department of Neuromuscular Research, National Institute of Neuroscience, Kodaira, 187-8502, Japan

    Ichizo Nishino

  4. Department of Pediatrics, Keio University School of Medicine, Tokyo, 160-8582, Japan

    Tomonobu Hasegawa

  5. Department of Molecular Medicine and Surgery, Karolinska University Hospital, Stockholm, Sweden

    Agneta Nordenskjöld

  6. Dipartimento di Patologia Umana ed Ereditaria, Sezione di Biologia Generale e Genetica Medica, Universita di Pavia, Pavia, 27100, Italia

    Giovanna Camerino

  7. Department of Molecular Pathology, Institut de Génétique et de Biologie Moléculaire et Cellulaire, Illkirch, 67404, France

    Christine Kretz, Anna Buj-Bello & Jocelyn Laporte

  8. Center for Animal Resources and Development, Kumamoto University School of Medicine, Kumamoto, 860-0811, Japan

    Gen Yamada

Authors
  1. Maki Fukami
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  2. Yuka Wada
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  3. Kanako Miyabayashi
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  5. Tomonobu Hasegawa
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  6. Agneta Nordenskjöld
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  9. Anna Buj-Bello
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  10. Jocelyn Laporte
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  11. Gen Yamada
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  12. Ken-ichirou Morohashi
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  13. Tsutomu Ogata
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Contributions

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.

Corresponding author

Correspondence to Tsutomu Ogata.

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Competing interests

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). https://doi.org/10.1038/ng1900

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