Clinical correlation between premature ovarian failure and a chromosomal anomaly in a 22-year-old Caucasian woman: a case report

Dell'Edera, Domenico; Tinelli, Andrea; Capozzi, Oronzo; Epifania, Annunziata Anna; Malvasi, Antonio; Lofrese, Dominga; Pacella, Elena; Milazzo, G.; Mazzone, Eleonora; Leo, M. Di; Rocchi, Mariano

doi:10.1186/1752-1947-6-368

Cited by 3 publications

(3 citation statements)

References 14 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…135,141 Within these regions, genes are present that are known to contribute to ovarian function including FMR1 (q27.3), inactive X-specific transcripts ( XIST ; q13.2), diaphanous homolog 2 ( DIAPH2 ; q21.33), BMP15 (p11.2), and X-linked inhibitor of apoptosis ( XIAP ; q25). Translocations of the X chromosome with other autosomes have also been found in patients with POI, including chromosomes 1, 123,142 2, 143,144 9, 123,135,144 11, 145 13, 143 14, 146 15, 147,148 18, 149 19, 143,144 22, 150 and Y. 143,144,151 Translocations between autosomes have also been identified in women with POI.…”

Section: Syndromic Pathologies That Diminish Ovarian Reservesmentioning

confidence: 99%

Genomic Markers of Ovarian Reserve

Wood¹,

Rajkovic

2013

Semin Reprod Med

View full text Add to dashboard Cite

Ovarian reserve and its utilization, over a reproductive life span, are determined by genetic, epigenetic, and environmental factors. The establishment of the primordial follicle pool and the rate of primordial follicle activation have been under intense study to determine genetic factors that affect reproductive lifespan. Much has been learned from transgenic animal models about the developmental origins of the primordial follicle pool and mechanisms that lead to primordial follicle activation, folliculogenesis, and the maturation of a single oocyte with each menstrual cycle. Recent genome-wide association studies on the age of human menopause have identified approximately 20 loci, and shown the importance of factors involved in double-strand break repair and immunology. Studies to date from animal models and humans show that many genes determine ovarian aging, and that there is no single dominant allele yet responsible for depletion of the ovarian reserve. Personalized genomic approaches will need to take into account the high degree of genetic heterogeneity, family pedigree, and functional data of the genes critical at various stages of ovarian development to predict women's reproductive life span.

show abstract

Section: Syndromic Pathologies That Diminish Ovarian Reservesmentioning

confidence: 99%

Genomic Markers of Ovarian Reserve

Wood¹,

Rajkovic

2013

Semin Reprod Med

View full text Add to dashboard Cite

show abstract

“…Even though females with intact X chromosomes usually present a random choice of which one becomes inactivated, in females that carry structural alterations on the X chromosome, cells with the least genomic imbalances are positively selected, which commonly results in a skewed inactivation (Podolska et al, 2017; Schluth et al, 2006). In X‐autosome translocations, which affect 1 in 30,000 live births (Dell'Edera et al, 2012), the skewness of XCI depends on whether the translocation is balanced or unbalanced (Leppig & Disteche, 2001). While in balanced X‐autosome rearrangements, the normal X is usually inactivated (Kalz‐Fuller et al, 1999; Schluth et al, 2006), in cases of unbalanced translocations, the derivative chromosome usually undergoes inactivation (Disteche et al, 1984; Schluth et al, 2006; Sisdelli et al, 2015; White et al, 1998).…”

Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 99%

Spread of X‐chromosome inactivation into autosomal regions in patients with unbalanced X‐autosome translocations and its phenotypic effects

Favilla

Meloni

Perez

et al. 2021

American J of Med Genetics Pt A

View full text Add to dashboard Cite

Patients with unbalanced X-autosome translocations are rare and usually present a skewed X-chromosome inactivation (XCI) pattern, with the derivative chromosome being preferentially inactivated, and with a possible spread of XCI into the autosomal regions attached to it, which can inactivate autosomal genes and affect the patients' phenotype. We describe three patients carrying different unbalanced X-autosome translocations, confirmed by G-banding karyotype and array techniques. We analyzed their XCI pattern and inactivation spread into autosomal regions, through HUMARA, ZDHHC15 gene assay and the novel 5-ethynyl-2 0 -deoxyuridine (EdU) incorporation assay, and identified an extremely skewed XCI pattern toward the derivative chromosomes for all the patients, and a variable pattern of late-replication on the autosomal regions of the derivative chromosomes. All patients showed phenotypical overlap with patients presenting deletions of the autosomal late-replicating regions, suggesting that the inactivation of autosomal segments may be responsible for their phenotype. Our data highlight the importance of the XCI spread into autosomal regions for establishing the clinical picture in patients carrying unbalanced X-autosome translocations, and the incorporation of EdU as a novel and precise tool to evaluate the inactivation status in such patients.

show abstract

Premature ovarian insufficiency is associated with global alterations in the regulatory landscape and gene expression in balanced X-autosome translocations

Di-Battista

Favilla

Zamariolli

et al. 2023

Epigenetics & Chromatin

View full text Add to dashboard Cite

Background Patients with balanced X-autosome translocations and premature ovarian insufficiency (POI) constitute an interesting paradigm to study the effect of chromosome repositioning. Their breakpoints are clustered within cytobands Xq13–Xq21, 80% of them in Xq21, and usually, no gene disruption can be associated with POI phenotype. As deletions within Xq21 do not cause POI, and since different breakpoints and translocations with different autosomes lead to this same gonadal phenotype, a “position effect” is hypothesized as a possible mechanism underlying POI pathogenesis. Objective and methods To study the effect of the balanced X-autosome translocations that result in POI, we fine-mapped the breakpoints in six patients with POI and balanced X-autosome translocations and addressed gene expression and chromatin accessibility changes in four of them. Results We observed differential expression in 85 coding genes, associated with protein regulation, multicellular regulation, integrin signaling, and immune response pathways, and 120 differential peaks for the three interrogated histone marks, most of which were mapped in high-activity chromatin state regions. The integrative analysis between transcriptome and chromatin data pointed to 12 peaks mapped less than 2 Mb from 11 differentially expressed genes in genomic regions not related to the patients’ chromosomal rearrangement, suggesting that translocations have broad effects on the chromatin structure. Conclusion Since a wide impact on gene regulation was observed in patients, our results observed in this study support the hypothesis of position effect as a pathogenic mechanism for premature ovarian insufficiency associated with X-autosome translocations. This work emphasizes the relevance of chromatin changes in structural variation, since it advances our knowledge of the impact of perturbations in the regulatory landscape within interphase nuclei, resulting in the position effect pathogenicity.

show abstract

Clinical correlation between premature ovarian failure and a chromosomal anomaly in a 22-year-old Caucasian woman: a case report

Cited by 3 publications

References 14 publications

Genomic Markers of Ovarian Reserve

Genomic Markers of Ovarian Reserve

Spread of X‐chromosome inactivation into autosomal regions in patients with unbalanced X‐autosome translocations and its phenotypic effects

Premature ovarian insufficiency is associated with global alterations in the regulatory landscape and gene expression in balanced X-autosome translocations

Contact Info

Product

Resources

About