title: Is there a Mendelian transmission ratio distortion of the c.429_452dup(24bp) polyalanine tract ARX mutation?
abstract: 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.
authors.affiliation: Neurogenetics Laboratory, Department of Genetics and Molecular Pathology, SA Pathology at the Women's and Children's Hospital, North Adelaide, South Australia, Australia. cheryl.shoubridge@adelaide.edu.au
authors.forename: Cheryl
authors.initials: C
authors.lastname: Shoubridge
authors.forename: Alison
authors.initials: A
authors.lastname: Gardner
authors.forename: Charles E
authors.initials: CE
authors.lastname: Schwartz
authors.forename: Anna
authors.initials: A
authors.lastname: Hackett
authors.forename: Michael
authors.initials: M
authors.lastname: Field
authors.forename: Jozef
authors.initials: J
authors.lastname: Gecz
mesh_terms: D000409:Alanine / Q000235:genetics; D005260:Female; D006579:Heterozygote; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D040582:Inheritance Patterns / Q000235:genetics*; D008297:Male; D008540:Meiosis / Q000235:genetics; D009154:Mutation; D009865:Oocytes; D010375:Pedigree; D012091:Repetitive Sequences, Nucleic Acid / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics*
chemical_list: C469264:ARX protein, human; D018398:Homeodomain Proteins; D014157:Transcription Factors; D000409:Alanine