Exome sequencing revealed a novel nonsense variant in ALX3 gene underlying frontorhiny

J Hum Genet. 2018 Jan;63(1):97-100. doi: 10.1038/s10038-017-0358-y. Epub 2017 Nov 16.


Frontorhiny is one of the two forms of mid-facial malformations characterized by ocular hypertelorism, wide and short nasal ridge, bifid nasal tip, broad columella, widely separated nares, long and wide philtrum and V-shaped hairline. Sometimes these phenotypes are associated with ptosis and midline dermoid cysts. Frontorhiny inherits in an autosomal recessive pattern. Sequence variants in the Aristaless-like homeobox 3 (ALX3) gene underlying frontorhiny have been reported previously. Here, in the present study, we have investigated four patients in a consanguineous family of Pakistani origin segregating frontorhiny in autosomal recessive manner. Genome scan using 250k Nsp1 array followed by exome and Sanger sequence analysis revealed a novel homozygous nonsense variant (c.604C>T, p.Gln202*) in the ALX3 gene resulting in frontorhiny in the family. This is the first mutation in the ALX3 gene, underlying frontorhiny, in Pakistani population.

Publication types

  • Clinical Trial

MeSH terms

  • Codon, Nonsense*
  • Craniofacial Abnormalities / genetics*
  • Craniofacial Abnormalities / pathology
  • DNA Mutational Analysis
  • Exome*
  • Face / abnormalities*
  • Face / pathology
  • Family
  • Female
  • Homeodomain Proteins / genetics*
  • Humans
  • Male
  • Pakistan
  • Pedigree


  • ALX3 protein, human
  • Codon, Nonsense
  • Homeodomain Proteins

Supplementary concepts

  • Frontonasal dysplasia