title: Variations of the Amnionless gene in recurrent spontaneous abortions.
abstract: Recurrent spontaneous abortions (RSA) are estimated to affect 0.5-1% of couples trying to have a child. The causes of RSA are unknown in the majority of cases. This study aimed to determine whether homozygous mutations in the AMN gene in a fetus cause spontaneous abortions in humans, as they are known to cause spontaneous abortions in mice. The study was conducted by screening 40 couples and 5 women with three or more unexplained spontaneous abortions for heterozygous mutations in the AMN gene using denaturing high-performance liquid chromatography. Altogether, 3 exonic and 11 intronic sequence variations were found. There were no significant differences in the frequencies of the variations between the patients and a control group. One of the exonic variations was non-synonymous, and three of the variations may affect gene splicing. None of the putative phenotype-affecting variations were found in both partners in any couple. These results indicate that RSA in the couples studied cannot be explained by homozygous AMN mutations in the fetus. However, two couples had different, potentially deleterious variations in both partners. If these variations have a phenotypic effect, the RSA experienced by these couples may be caused by mutations in the AMN gene. In addition, birthplaces of the patients' ancestors revealed some clustering, suggesting that some patients may carry a founder mutation in another gene which may contribute to RSA.
authors.affiliation: Folkhälsan Institute of Genetics, University of Helsinki, Finland. milja.kaare@helsinki.fi
authors.forename: Milja
authors.initials: M
authors.lastname: Kaare
authors.forename: Jodie N
authors.initials: JN
authors.lastname: Painter
authors.forename: Veli-Matti
authors.initials: VM
authors.lastname: Ulander
authors.forename: Risto
authors.initials: R
authors.lastname: Kaaja
authors.forename: Kristiina
authors.initials: K
authors.lastname: Aittomäki
mesh_terms: D000026:Abortion, Habitual / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D000650:Amnion / Q000502:physiology; D000818:Animals; D005260:Female; D014644:Genetic Variation; D006801:Humans; D008565:Membrane Proteins; D011506:Proteins / Q000235:genetics*; D012008:Recurrence
chemical_list: C484714:AMN protein, human; D008565:Membrane Proteins; D011506:Proteins