Neurogenetics Laboratory, Department of Genetics and Molecular Pathology, SA Pathology at the Women's and Children's Hospital, North Adelaide, South Australia, Australia.
Eur J Hum Genet. 2012 Dec;20(12):1311-4. doi: 10.1038/ejhg.2012.61. Epub 2012 Apr 11.
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.
智力障碍很常见。Aristoless 相关同源盒（ARX）基因是最常突变和多效的基因之一，与 10 种不同的表型有关。超过一半的~100 例报道的 ARX 基因突变病例是由于 24bp 的重复，c.429_452dup，导致多聚丙氨酸链的扩展。常染色体隐性携带者女性的后代中受累男性明显偏多，这使得 c.429_452dup 突变的传递比发生了偏差。我们发现，c.429_452dup ARX 突变的传递明显偏离了预期的孟德尔 1:1 比例，有利于该突变。我们假设 c.429_452dup 突变的优先传递可能是由于卵母细胞减数分裂的不对称性所致。我们的发现可能对携带 c.429_452dup 突变的家庭的遗传咨询具有重要意义，并暗示 ARX 在卵母细胞生物学中的潜在作用。
