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

Abstract

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.

Noninvasive prenatal screening for fetal aneuploidy, 2016 update: a position statement of the American College of Medical Genetics and Genomics

“…Conventional screening for aneuploidies does not detect sex chromosome aneuploidies. The most common of these, monosomy X (Turner syndrome), has been estimated to occur in 1-1.5% of pregnancies 51 and is a common cause of firsttrimester pregnancy loss (~23%). 52 The phenotype of individuals with a 47,XXX or 47,XYY karyotype is highly variable but may include social or cognitive deficits.…”

Síndrome de Turner, Tireoidite de Hashimoto e doença de Crohn em irmãs: relato de caso

“…A ST também está associada a algumas anomalias médicas, como anormalidades cardiovasculares e renais, distúrbios da tireoide, perda de audição, hipertensão arterial, osteoporose e infertilidade 14 . Além disso, sabe-se que a autoimunidade está aumentada nesta síndrome 15,16 .…”

Current status of non-invasive prenatal testing (NIPT): genetic counseling, dominant methods and overall performance

“…Second, feto-placental and maternal mosaicism is more frequent for SCAs: it has been demonstrated, that with advanced maternal age, the mosaic loss of a single maternal X-chromosome is more likely [44,45]. Additionally, placental mosaicism is observed in around 60% of Turner syndrome neonates [46,47]. Third, prenatally obtained fetal sex information can favor unethical sex selection, if not prohibited by legal obligations.…”