Turner syndrome revisited: review of new data supports the hypothesis that all viable 45,X cases are cryptic mosaics with a rescue cell line, implying an origin by mitotic loss.

We review the data pertinent to the hypothesis we proposed three decades ago, that all embryos that survive gestation as women with Turner syndrome and have an ostensibly non-mosaic 45,X karyotype, actually are cryptic mosaics for a "rescue line" that includes a viable karyotype. Reanalysis of the prevalence and frequency of 45,X in available data on spontaneous abortuses, and livebirths, confirms prior estimates that 1 % to 1.5 % of all recognizable pregnancies start as an apparent non-mosaic 45,X but about 99 % do not survive gestation. From the rates of 45,X in early embryos, which are notably higher than the inferred rate of gametes hypohaploid for a sex chromosome, as well as the negative maternal age association with 45,X of maternal origin we deduce, in agreement with but on independent grounds from Hall et al. (2006), that a very large proportion of 45,X embryos acquired their 45,X line after fertilization. Results of a search for mosaic cell lines in patients with "Turner syndrome" in several reports indicate that not only does the detection rate of a mosaic line depend upon the number and sensitivity of the markers used, and the number of different tissues examined, but also upon the severity of the phenotype of those cases studied, and the number of cells karyotyped initially. Such factors may explain variation in the extent of detected "cryptic" mosaicism in 45,X individuals (currently at least 50 %). We note a report by Urbach and Benvenitsy (2009) of a gene necessary for placental function, PSF2RA, which lies in the pseudoautosomal-one region of the X and Y chromosomes. Deletion of such a gene could account for the high embryonic lethality in 45,X conceptions, and a rescue line in the placenta could account for embryonic and fetal survival of those cases in which a cryptic mosaic line cannot be found in the usual studies of blood and other tissues from affected individuals. Our primary conclusions are 1) all 45,X individuals with Turner syndrome are cryptic mosaics, 2) absence of the X chromosome in 45,X embryos is caused primarily by mitotic factors, and 3) the placenta is a strong candidate for the location of the rescue line in apparently non-mosaic 45,X individuals.

Unequal adaptive value of changing cigarette use during pregnancy for heavy, moderate, and light smokers.

To determine the effects of changes in maternal cigarette use during pregnancy on birthweight, a sample of Caucasian births free of major malformations (n = 9,943) was examined. Births were stratified by level of maternal smoking in the first trimester and subdivided according to whether the mother continued at the same level, reduced, or quit by the second trimester. Birthweights were adjusted statistically for extraneous variables. As expected, second and third trimester cigarette use was associated with birthweight, but so too was cigarette use during the first trimester, and the effect of quitting varied significantly with the level of first trimester smoking. Among moderate and light smokers, who comprise the majority of smokers, quitting before the second trimester is associated with heavier infants. However, infants of heavy smokers who quit by the second trimester did not weigh significantly more than infants of mothers who continued to smoke heavily throughout pregnancy, and weighed significantly less than infants of nonsmokers or other smokers who quit. Thus, quitting by the end of the first trimester may not completely negate the effect of heavy first trimester smoking, and the adaptive value of qutting is unequal among different levels of first trimester smoking. Further research on prenatal growth should take cigarette smoking in all trimesters into account. © 1994 Wiley-Liss, Inc.