Loss-of-function mutations in HOXC13 cause pure hair and nail ectodermal dysplasia

Am J Hum Genet. 2012 Nov 2;91(5):906-11. doi: 10.1016/j.ajhg.2012.08.029. Epub 2012 Oct 11.


Pure hair and nail ectodermal dysplasia (PHNED) is a congenital condition characterized by hypotrichosis and nail dystrophy. Autosomal-recessive PHNED has previously been mapped to chromosomal region 12q12-q14.1, which contains the type II hair keratin and HOXC clusters. Hoxc13-null mice are known to develop hair and nail defects very similar to those seen in human PHNED. We performed whole-exome sequencing in a consanguineous Chinese family affected by PHNED and identified a homozygous nonsense mutation (c.390C>A [p.Tyr130(∗)]) in HOXC13 in all affected individuals. In an additional affected female from a consanguineous Afghan family, we found a 27.6 kb homozygous microdeletion involving the first exon of HOXC13. We examined HOXC13 expression in scalp specimen obtained from the index individual of the Chinese family and detected dramatically reduced mRNA levels in skin tissue and nearly absent protein staining in hair follicles, suggesting a mechanism of nonsense-mediated mRNA decay. We also observed markedly decreased expression of four HOXC13 target genes in the specimen. Taken together, our results demonstrate that loss-of-function mutations in HOXC13 cause autosomal-recessive PHNED and further highlight the importance of HOXC13 in hair and nail development.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Asian Continental Ancestry Group / genetics
  • China
  • Consanguinity
  • Ectodermal Dysplasia / genetics*
  • Ectodermal Dysplasia / pathology
  • Exome
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation
  • Genes, Recessive
  • Homeodomain Proteins / genetics*
  • Homozygote
  • Humans
  • Hypotrichosis / genetics*
  • Male
  • Mice
  • Mice, Transgenic
  • Nail Diseases / genetics*
  • Pedigree
  • Phenotype
  • Skin / pathology


  • HOXC13 protein, human
  • Homeodomain Proteins