Is there a Mendelian transmission ratio distortion of the c.429 -452dup(24bp) polyalanine tract ARX mutation?

Cheryl Shoubridge, Alison Gardner, Charles E. Schwartz, Anna Hackett, Michael Field, Jozef Gecz

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7 Citations (Scopus)


Intellectual disability is common. Aristaless-related homeobox (ARX) gene is one of the most frequently mutated and pleiotropic genes, implicated in 10 different phenotypes. More than half of ∼100 reported cases with ARX mutations are due to a recurrent duplication of 24 bp, c.429-452dup, which leads to polyalanine tract expansion. The excess of affected males among the offspring of the obligate carrier females raised the possibility of transmission ratio distortion for the c.429-452dup mutation. We found a significant deviation from the expected Mendelian 1:1 ratio of transmission in favour of the c.429-452dup ARX mutation. We hypothesise that the preferential transmission of the c.429-452dup mutation may be due to asymmetry of meiosis in the oocyte. Our findings may have implications for genetic counselling of families segregating the c.429-452dup mutation and allude to putative role of ARX in oocyte biology.

Original languageEnglish
Pages (from-to)1311-1314
Number of pages4
JournalEuropean Journal of Human Genetics
Issue number12
Publication statusPublished - 1 Dec 2012
Externally publishedYes


  • ARX
  • Mendelian transmission
  • intellectual disability
  • meiotic drive
  • polyalanine tract expansions

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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