Whole exome sequencing identifies three novel mutations in ANTXR1 in families with GAPO syndrome

Am J Med Genet A. 2014 Sep;164A(9):2328-34. doi: 10.1002/ajmg.a.36678. Epub 2014 Jul 14.


GAPO syndrome (OMIM#230740) is the acronym for growth retardation, alopecia, pseudoanodontia, and optic atrophy. About 35 cases have been reported, making it among one of the rarest recessive conditions. Distinctive craniofacial features including alopecia, rarefaction of eyebrows and eyelashes, frontal bossing, high forehead, mid-facial hypoplasia, hypertelorism, and thickened eyelids and lips make GAPO syndrome a clinically recognizable phenotype. While this genomic study was in progress mutations in ANTXR1 were reported to cause GAPO syndrome. In our study we performed whole exome sequencing (WES) for five affected individuals from three Turkish kindreds segregating the GAPO trait. Exome sequencing analysis identified three novel homozygous mutations including; one frame-shift (c.1220_1221insT; p.Ala408Cysfs*2), one splice site (c.411A>G; p.Gln137Gln), and one non-synonymous (c.1150G>A; p.Gly384Ser) mutation in the ANTXR1 gene. Our studies expand the allelic spectrum in this rare condition and potentially provide insight into the role of ANTXR1 in the regulation of the extracellular matrix.

Keywords: ANTXR1; GAPO syndrome; whole exome sequencing.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adolescent
  • Adult
  • Alopecia / genetics*
  • Anodontia / genetics*
  • Base Sequence
  • Child
  • Chromosome Segregation / genetics
  • DNA Mutational Analysis
  • Exome / genetics*
  • Facies
  • Family
  • Female
  • Growth Disorders / genetics*
  • Humans
  • Male
  • Microfilament Proteins
  • Molecular Sequence Data
  • Mutation / genetics*
  • Neoplasm Proteins / chemistry
  • Neoplasm Proteins / genetics*
  • Optic Atrophies, Hereditary / genetics*
  • Pedigree
  • Protein Structure, Tertiary
  • Receptors, Cell Surface / chemistry
  • Receptors, Cell Surface / genetics*


  • ANTXR1 protein, human
  • Microfilament Proteins
  • Neoplasm Proteins
  • Receptors, Cell Surface

Supplementary concepts

  • Growth retardation, Alopecia, Pseudoanodontia and Optic atrophy