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Mutations in X-linked PORCN, a putative regulator of Wnt signaling, cause focal dermal hypoplasia

Nature Genetics volume 39, pages 836–838 (2007)Cite this article

Abstract

Focal dermal hypoplasia is an X-linked dominant disorder characterized by patchy hypoplastic skin and digital, ocular and dental malformations. We used array comparative genomic hybridization to identify a 219-kb deletion in Xp11.23 in two affected females. We sequenced genes in this region and found heterozygous and mosaic mutations in PORCN in other affected females and males, respectively. PORCN encodes the human homolog of Drosophila melanogaster porcupine, an endoplasmic reticulum protein involved in secretion of Wnt proteins.

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Figure 1: Characterization of Xp11.23 deletion in individual G17 with FDH.

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Acknowledgements

We thank research subjects and their families for their participation in the research and all clinicians and genetic counselors who referred patients. We thank H.Y. Zoghbi and A.L. Beaudet for critical reading and discussions during preparation of this manuscript and L. Cooper, W. Jin and A. Casillas for technical assistance. This work was funded by the National Foundation for Ectodermal Dysplasias, in part by US National Institutes of Health (NIH) grant HD051805 and by the Tissue Culture Core, Genome Analysis Core and Gene Expression Core Laboratories of the Baylor College of Medicine Mental Retardation and Developmental Disabilities Research Center (NIH grant HD024064).

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Author notes

  1. Xiaoling Wang and V Reid Sutton: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Obstetrics and Gynecology, Baylor College of Medicine, Houston, 77030, Texas, USA

    Xiaoling Wang, Zhiyin Yu, Ying-Chuck Kou & Ignatia B Van den Veyver

  2. Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, 77030, Texas, USA

    V Reid Sutton, Tanya N Eble, Ankita Patel, Ping Fang & Ignatia B Van den Veyver

  3. Department of Pediatrics, Instituto Mexicano del Seguro Social (IMSS), Merida, 97109, Mexico

    J Omar Peraza-Llanes

  4. Department of Pediatrics, Baylor College of Medicine, Houston, 77030, Texas, USA

    Rebecca Rosetta

  5. Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, 77030, Texas, USA

    Christina Thaller

Authors
  1. Xiaoling Wang
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  2. V Reid Sutton
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  11. Ignatia B Van den Veyver
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Contributions

X.W. contributed to array CGH, mutation analysis, qPCR and cell culture. V.R.S. contributed to research subject enrollment, clinical evaluation, manuscript writing and data analysis. J.O.P.-L. referred and evaluated individual G17, critical to the identification of the gene associated with FDH. Z.Y. contributed to mutation analysis and DNA preparation. R.R. contributed to cell culture and DNA preparation. Y.-C.K. contributed to qPCR. T.N.E. coordinated research and maintained the research subject database. C.T. contributed to RNA in situ hybridization. A.P. contributed to FISH. P.F. contributed to X chromosome inactivation studies. I.B.V.d.V. oversaw all aspects of the research and contributed to manuscript writing.

Corresponding author

Correspondence to Ignatia B Van den Veyver.

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Competing interests

The authors declare no competing financial interests.

Supplementary information

Supplementary Fig. 1

Phenotype of an individual with FDH with an Xp11.23 deletion, and array CGH hybridization results on DNA from her parents. (PDF 63 kb)

Supplementary Fig. 2

Mutations in PORCN. (PDF 351 kb)

Supplementary Fig. 3

X chromosome inactivation plots. (PDF 71 kb)

Supplementary Fig. 4

Copy number analysis and X chromosome inactivation studies on male samples, and sequencing profiles for male G248. (PDF 117 kb)

Supplementary Fig. 5

Xp11.23 deletion in G43. (PDF 37 kb)

Supplementary Fig. 6

Expression of Porcn mRNA in mouse embryos. (PDF 165 kb)

Supplementary Table 1

Summary of reported phenotypic features. (PDF 45 kb)

Supplementary Methods (PDF 50 kb)

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Wang, X., Reid Sutton, V., Omar Peraza-Llanes, J. et al. Mutations in X-linked PORCN, a putative regulator of Wnt signaling, cause focal dermal hypoplasia. Nat Genet 39, 836–838 (2007). https://doi.org/10.1038/ng2057

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