X chromosome inactivation patterns in 45,X/46,XX mosaics

Abstract

To investigate X chromosome inactivation (XCI) patterns in 45,X/46,XX mosaics, genomic DNA was extracted from peripheral blood samples of 15 female subjects who showed different proportions of 45,X cell clones. XCI patterns were analyzed using two assays. The first assay was the BstXI restriction endonuclease detection of an Xlinked phosphoglycerate kinase (PGK) gene polymorphism following digestion of the DNA with methylation-sensitive HpaII, or with methylation-insensitive AfaI as a control. The second assay was the detection of a CAG triplet repeat polymorphism in the X-linked androgen receptor (AR) gene after sodium bisulfite treatment. Of the 15 subjects, 11 were informative due to heterozygosity for at least one of the polymorphisms (6 were heterozygous for the PGK polymorphism and 9 were heterozygous for the AR polymorphism). Four of the 11 informative subjects (36%) showed extremely skewed XCI for at least one of the polymorphisms, which was a much higher incidence than previously reported for normal females. Moreover, 3 of these 4 women had proportions of 45,X cell clones greater than 20%. Although our results may be due to several possible cytogenetic or molecular mechanisms, the most likely explanation is that cases of 45,X/46,XX that contain relatively high levels of 45,X cell clones probably arose due to structural aberrations of the X chromosome undetectable by conventional karyotyping.

Genetic significance of skewed X‐chromosome inactivation in premature ovarian failure

“…Skewed XCI possibly takes place in extraembryonic tissues of normal conceptuses [Uehara et al, 2000], in women with structurally aberrant X‐chromosomes [Therman and Patau, 1974; Heard et al, 1997] and in 45,X/46,XX mosaics [Uehara et al, 2001b]. Furthermore, Busque et al [1996], who analyzed skewed XCI, described that as the incidence increased with age, the incidence in neonates corresponded to truly skewed XCI.…”

“…Several methods for evaluating XCI patterns are based on the assessment of differential methylation of CpG dinucleotides between active and inactive X‐chromosomes. To achieve this, X‐linked genes with known nucleotide polymorphisms have been used, including a Bst XI site polymorphism within intron 1 of the phosphoglycerate kinase gene [Vogelstein et al, 1987; Uehara et al, 2000] and a CAG triplet repeat [(CAG) n ] polymorphism within exon 1 of the androgen receptor gene ( AR ) [Kubota et al, 1999; Uehara et al, 2001a,b]. To assess differential methylation, samples are first treated with a methylation‐sensitive endonuclease or sodium bisulfite, and then PCR‐amplified.…”

Progressive morphea of early childhood tracing Blaschko’s lines on the face: involvement of X chromosome monosomy in pathogenesis and clinical prognosis

“…In this report, a five-year-old girl with Turner's stigmata similar to those of our patient also showed extreme XCI. 21 X chromosome inactivation patterns were assessed in 70 female patients with SSc in order to ascertain the role of XCI in the predisposition of women to autoimmunity. XCI status was found to be informative in 55 of the 70 SSc patients and in 124 of the 160 controls.…”

Role of polymorphism of the androgen receptor gene and non-random X chromosome inactivation in the genesis of androgenic alopecia in women of childbearing potential

“…В норме у лиц женского пола наблюдается случайная инактивация Х-хромосомы, что обеспечивает функционирование лишь одного из Х-сцепленных генов [15,16]. Неслучайная xCI наблюдается в норме в экстраэмбриональных тканях, а также при некоторых патологических состояниях [16][17][18][19][20][21][22].…”