Mutations in R-spondin 4 (RSPO4) underlie inherited anonychia.
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.
Ishii
Yoshiyuki
Y
Department of Dermatology, Columbia University, New York, New York, USA.
Wajid
Muhammad
M
Bazzi
Hisham
H
Fantauzzo
Katherine A
KA
Barber
Alison G
AG
Blaydon
Diana C
DC
Nam
Ju-Suk
JS
Yoon
Jeong K
JK
Kelsell
David Peter
DP
Christiano
Angela M
AM
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