Parental origin of normal X chromosomes in Turner syndrome patients with various karyotypes: Implications for the mechanism leading to generation of a 45,X karyotype

Abstract

The parental origin of the X chromosome of 45,X females has been the subject of many studies, and most of them have shown that the majority (60-80%) of the X chromosomes are maternal in origin. However, studies on the parental origin of normal X chromosomes are relatively limited for Turner syndrome (TS) females with sex chromosome aberrations. In this study, we used PCR-based typing of highly polymorphic markers and an assay of methylation status of the androgen receptor gene to determine the parental origin of normal X chromosomes in 50 unbiased TS females with a variety of karyotypes. Our results showed a higher paternal meiotic error rate leading to the generation of abnormal sex chromosomes, especially in the case of del(Xp) and abnormal Y chromosomes. Isochromosome Xq and ring/marker X chromosomes, on the other hand, were equally likely the result of both maternal and paternal meiotic errors. A thorough review of previous results, together with our data suggests, that the majority of TS karyotype are caused by paternal meiotic errors that generate abnormal sex chromosomes, and that most 45,X cells are generated by mitotic loss of these abnormal sex chromosomes, resulting in maternal X dominance in these cells.

Prader–Willi syndrome and Tay–Sachs disease in association with mixed maternal uniparental isodisomy and heterodisomy 15 in a girl who also had isochromosome Xq

“…SNP trio analysis using samples from the patient and parents is consistent with a single X chromosome inherited from the father and an i(X)(q10) of maternal origin. Parental age effects have not been associated with isochromosomes [James et al, 1997;Uematsu et al, 2002]. Although the isochromosome Xq and the maternal UPD(15) were both maternal in origin, there is no clear relationship between the two events.…”

Incidence of non-age-dependent chromosomal abnormalities: a population-based study on 88965 amniocenteses

“…Molecular studies of 45,X karyotypes show that the single X chromosome is maternally derived in about 80% of the cases, probably due to a higher risk of mispairing between the X and Y chromosomes during male meiosis, as well as a greater tendency to mitotic loss of a Y chromosome compared with an X chromosome. 17 Therefore, the postzygotic loss of the Y chromosome as a mechanism of the 45,X/46,XY may well explain why this karyotype is not influenced by the age of the mother.…”

Prenatal Diagnosis and Management of Monozygotic Twins Discordant for Turner Syndrome

“…Some patients pregnant with abnormal twins terminated pregnancies without prenatal karyotyping and zygosity analysis. Turner syndrome is reported to approach 99% in singletons [7] ; some cases of a 'vanished' twin or IUFD of one twin may be the result of a nonviable chromosomal abnormality.…”

“…Abnormalities of chromosomes X, Y, 13, 18 and 21 are most commonly detected by fluorescence in situ hybridization. Uematsu et al [7] reported that the majority of Turner syndrome patients are maternal X dominant in 45,X cells, which results from mitotic loss of abnormal paternal idiochromosomes. Idiochromosome loss in a few cells after fertilization in early embryology may trigger Turner syndrome discordant twinning.…”