A novel X chromosome–linked genetic cause of recurrent spontaneous abortion

Lanasa, Mark C.; Hogge, W. Allen; Kubik, Carolyn J.; Ness, Roberta B.; Harger, James H.; Nagel, Theodore C.; Prosen, Tracy L.; Marković, Nina; Hoffman, Eric P.

doi:10.1067/mob.2001.117670

Cited by 57 publications

(59 citation statements)

References 14 publications

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“…In modeling these data, Lanasa et al (33) suggested that the female carrier undergoes selective inactivation of the normal X chromosome; the remaining abnormal active X chromosome in a conceptus would be aborted. Confirmatory studies by these investigators are consistent with the initial hypothesis (34). Fewer boy children were born to female carriers.…”

Section: Sex and Sex Ratio Of Children Born To Applicator Familiessupporting

confidence: 79%

Birth defects, season of conception, and sex of children born to pesticide applicators living in the Red River Valley of Minnesota, USA.

Garry

Harkins

Erickson

et al. 2002

Environ Health Perspect

205

119

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We previously demonstrated that the frequency of birth defects among children of residents of the Red River Valley (RRV), Minnesota, USA, was significantly higher than in other major agricultural regions of the state during the years 1989-1991, with children born to male pesticide applicators having the highest risk. The present, smaller cross-sectional study of 695 families and 1,532 children, conducted during 1997-1998, provides a more detailed examination of reproductive health outcomes in farm families ascertained from parent-reported birth defects. In the present study, in the first year of life, the birth defect rate was 31.3 births per 1,000, with 83% of the total reported birth defects confirmed by medical records. Inclusion of children identified with birth or developmental disorders within the first 3 years of life and later led to a rate of 47.0 per 1,000 (72 children from 1,532 live births). Conceptions in spring resulted in significantly more children with birth defects than found in any other season (7.6 vs. 3.7%). Twelve families had more than one child with a birth defect (n = 28 children). Forty-two percent of the children from families with recurrent birth defects were conceived in spring, a significantly higher rate than that for any other season. Three families in the kinships defined contributed a first-degree relative other than a sibling with the same or similar birth defect, consistent with a Mendelian inheritance pattern. The remaining nine families did not follow a Mendelian inheritance pattern. The sex ratio of children with birth defects born to applicator families shows a male predominance (1.75 to 1) across specific pesticide class use and exposure categories exclusive of fungicides. In the fungicide exposure category, normal female births significantly exceed male births (1.25 to 1). Similarly, the proportion of male to female children with birth defects is significantly lower (0.57 to 1; p = 0.02). Adverse neurologic and neurobehavioral developmental effects clustered among the children born to applicators of the fumigant phosphine (odds ratio [OR] = 2.48; confidence interval [CI], 1.2-5.1). Use of the herbicide glyphosate yielded an OR of 3.6 (CI, 1.3-9.6) in the neurobehavioral category. Finally, these studies point out that (a) herbicides applied in the spring may be a factor in the birth defects observed and (b) fungicides can be a significant factor in the determination of sex of the children of the families of the RRV. Thus, two distinct classes of pesticides seem to have adverse effects on different reproductive outcomes. Biologically based confirmatory studies are needed.

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Section: Sex and Sex Ratio Of Children Born To Applicator Familiessupporting

confidence: 79%

Birth defects, season of conception, and sex of children born to pesticide applicators living in the Red River Valley of Minnesota, USA.

Garry

Harkins

Erickson

et al. 2002

Environ Health Perspect

205

119

View full text Add to dashboard Cite

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“…S pontaneous abortions can be triggered by maternal and fetal pathologies (1)(2)(3)(4)(5)(6) or immunological incompatibilities (7)(8)(9)(10)(11). However, pathologies and incompatibilities alone do not explain all miscarriages (12).…”

mentioning

confidence: 99%

Cortisol levels and very early pregnancy loss in humans

Nepomnaschy

Welch

McConnell

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

279

197

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Maternal stress is commonly cited as an important risk factor for spontaneous abortion. For humans, however, there is little physiological evidence linking miscarriage to stress. This lack of evidence may be attributable to a paucity of research on maternal stress during the earliest gestational stages. Most human studies have focused on ''clinical'' pregnancy (>6 weeks after the last menstrual period). The majority of miscarriages, however, occur earlier, within the first 3 weeks after conception (Ϸ5 weeks after the last menstrual period). Studies focused on clinical pregnancy thus miss the most critical period for pregnancy continuance. We examined the association between miscarriage and levels of maternal urinary cortisol during the first 3 weeks after conception. Pregnancies characterized by increased maternal cortisol during this period (within participant analyses) were more likely to result in spontaneous abortion (P < 0.05). This evidence links increased levels in this stress marker with a higher risk of early pregnancy loss in humans.stress ͉ miscarriage ͉ placentation ͉ fetomaternal conflict ͉ evolutionary theory

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“…Of these X-linked diseases, 30% (149/387) are not mapped to a mutation in a specific gene. In addition, embryonic lethal mutations in X-linked genes are thought to underlie the preferential loss of male embryos in many cases of recurrent spontaneous abortion (RSA) (Pegoraro et al 1997;Lanasa et al 2001). Clearly, there is a need to better understand the function of genes on the X chromosome in order to link them to the full range of human X-linked disorders.…”

mentioning

confidence: 99%

Phenotypic annotation of the mouse X chromosome

Cox

Vollmer

Tamplin³

et al. 2010

Genome Res.

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Mutational screens are an effective means used in the functional annotation of a genome. We present a method for a mutational screen of the mouse X chromosome using gene trap technologies. This method has the potential to screen all of the genes on the X chromosome without establishing mutant animals, as all gene-trapped embryonic stem (ES) cell lines are hemizygous null for mutations on the X chromosome. Based on this method, embryonic morphological phenotypes and expression patterns for 58 genes were assessed, ∼10% of all human and mouse syntenic genes on the X chromosome. Of these, 17 are novel embryonic lethal mutations and nine are mutant mouse models of genes associated with genetic disease in humans, including BCOR and PORCN. The rate of lethal mutations is similar to previous mutagenic screens of the autosomes. Interestingly, some genes associated with X-linked mental retardation (XLMR) in humans show lethal phenotypes in mice, suggesting that null mutations cannot be responsible for all cases of XLMR. The entire data set is available via the publicly accessible website (http://xlinkedgenes.ibme.utoronto.ca/).

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A novel X chromosome–linked genetic cause of recurrent spontaneous abortion

Cited by 57 publications

References 14 publications

Birth defects, season of conception, and sex of children born to pesticide applicators living in the Red River Valley of Minnesota, USA.

Birth defects, season of conception, and sex of children born to pesticide applicators living in the Red River Valley of Minnesota, USA.

Cortisol levels and very early pregnancy loss in humans

Phenotypic annotation of the mouse X chromosome

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