A novel de novo 27 bp duplication of the ARX gene, resulting from postzygotic mosaicism and leading to three severely affected males in two generations

Orit Reish, Tod Fullston, Miriam Regev, Eli Heyman, Jozef Gecz

Research output: Contribution to journalArticlepeer-review

16 Citations (Scopus)


The Aristaless Related Homeobox (ARX) gene is a Q50 paired homeobox gene. These genes are important regulators of essential events during vertebrate embryogenesis, including the development of the central and peripheral nervous system. Mutations in ARX have been identified in at least 82 different families and sporadic cases, and are responsible for at least 8 clinically distinct disorders. The recurrent 24 bp duplication (dup) mutation, c.429-452dup(24 bp), is the most frequent ARX mutation, which accounts for 45% of all cases reported to date. Here we report a novel de novo, familial dup mutation of 27 bp, c.430-456dup(27 bp), which involves the same region of the ARX gene in exon 2, as the dup24 bp mutation. The female progenitor of this dup27 bp allele exhibitsmosaicism, likely resulting froma postmitotic de novo mutation event early in embryonic development. Three males with the dup27 bp mutation presented with infantile spasms, two ofwhom died early in life. Their phenotype appearedmore severe,whencompared to the spectrum of clinical presentations associated with the dup24 bp mutation. We propose that this might be at least partly due to the single, extra alanine residue (A) (21A in dup27 vs. 20A in dup24), which takes polyalanine tract 2 of ARX beyond the maximum, naturally occurring limit of 20A found in the human genome.

Original languageEnglish
Pages (from-to)1655-1660
Number of pages6
JournalAmerican Journal of Medical Genetics, Part A
Issue number8
Publication statusPublished or Issued - Aug 2009
Externally publishedYes


  • 27 bp duplication
  • ARX
  • Infantile spasms
  • Mosaicism
  • Polyalanine tract

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this