title: Mutations in R-spondin 4 (RSPO4) underlie inherited anonychia.
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.
authors.affiliation: Department of Dermatology, Columbia University, New York, New York, USA.
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Ishii
authors.forename: Muhammad
authors.initials: M
authors.lastname: Wajid
authors.forename: Hisham
authors.initials: H
authors.lastname: Bazzi
authors.forename: Katherine A
authors.initials: KA
authors.lastname: Fantauzzo
authors.forename: Alison G
authors.initials: AG
authors.lastname: Barber
authors.forename: Diana C
authors.initials: DC
authors.lastname: Blaydon
authors.forename: Ju-Suk
authors.initials: JS
authors.lastname: Nam
authors.forename: Jeong K
authors.initials: JK
authors.lastname: Yoon
authors.forename: David Peter
authors.initials: DP
authors.lastname: Kelsell
authors.forename: Angela M
authors.initials: AM
authors.lastname: Christiano
mesh_terms: D020405:Dermis / Q000378:metabolism; D005091:Exons / Q000235:genetics; D005260:Female; D006720:Homozygote; D006801:Humans; D007438:Introns / Q000235:genetics; D008297:Male; D009154:Mutation; D009264:Nails, Malformed / Q000235:genetics*; D010375:Pedigree; D022821:RNA Splice Sites / Q000235:genetics; D019699:Thrombospondins / Q000235:genetics* / Q000378:metabolism; D000098907:R-Spondins