1. ¹Department of Dermatology, Columbia University, New York, New York, USA
2. ²Department of Genetics and Development, Columbia University, New York, New York, USA
3. ³Centre for Cutaneous Research, Institute of Cell and Molecular Science, Queen Mary's School of Medicine and Dentistry, Queen Mary, University of London, Whitechapel, London, UK
4. ⁴Center for Molecular Medicine, Maine Medical Center Research Institute, Scarborough, Maine, USA

Correspondence: Dr Angela M. Christiano, Departments of Dermatology and Genetics and Development, Columbia University, College of Physicians and Surgeons, 630 West 168th Street, VC-15-204a, New York, New York 10032, USA. E-mail: amc65@columbia.edu

Received 8 January 2007; Revised 17 April 2007; Accepted 1 May 2007; Published online 6 September 2007.

Abstract

Recently, we reported that mutations in the R-spondin 4 (RSPO4) gene underlie inherited anonychia/hyponychia. Here, we studied five consanguineous Pakistani families with recessive inheritance of a combination of anonychia and hyponychia. Homozygous mutations were identified in the RSPO4 gene in all five families. Three families had a splice site mutation at the exon 2–intron 2 boundary. One family had a 26 bp deletion encompassing the start codon, and the final family had a missense mutation changing the initiating methionine to isoleucine. We demonstrated by in situ hybridization that Rspo4 is exclusively expressed in the mesenchyme underlying the digit tip epithelium in the mouse at embryonic day 14.5 (e14.5). These findings expand our understanding of the role of RSPO4 in nail development and disease.