Mutations in R-Spondin 4 (RSPO4) underlie inherited anonychia
Mutations in R-Spondin 4 (RSPO4) underlie inherited anonychia
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DOI：
10.1038/sj.jid.5701078
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发表时间：
2008-04-01
影响因子：
6.5
通讯作者：
Christiano, Angela M.
中科院分区：
文献类型：
--
作者：
Ishii, Yoshiyuki;Wajid, Muhammad;Christiano, Angela M.
最近，我们报道了 R-spondin 4 (RSPO4) 基因的突变是遗传性无甲/低甲的基础。在这里，我们研究了五个患有无甲症和低甲症隐性遗传的巴基斯坦近亲家庭。所有五个家族的 RSPO4 基因均发现纯合突变。三个家族在外显子2-内含子2边界处有剪接位点突变。其中一个家族存在包含起始密码子的 26 bp 缺失，最后一个家族存在错义突变，将起始蛋氨酸变为异亮氨酸。我们通过原位杂交证明，Rspo4 只在胚胎 14.5 天（e14.5）的小鼠指尖上皮下方的间充质中表达。这些发现扩展了我们对 RSPO4 在指甲发育和疾病中的作用的理解。
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.