Short stature and primary ovarian insufficiency possibly due to chromosomal position effect in a balanced X;1 translocation

Genesio, Rita; Mormile, Angela; Licenziati, Maria Rosaria; Brasi, Daniele De; Leone, Graziella; Balzano, Sara; Izzo, Antonella; Bonfiglio, Ferdinando; Conti, Anna; G, Fioretti; Lenta, S.; Poggiano, Maria Rita; Siani, Paolo; Nitsch, Lucio

doi:10.1186/s13039-015-0154-3

Cited by 13 publications

(10 citation statements)

References 31 publications

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“…DIAPH2 has been implicated in premature ovarian failure (POF2A, MIM: 300511), also known as primary ovarian insufficiency, which manifests as premature menopause [29][30][31][32][33][34]. The patients generally present translocations of the X chromosome region that includes DIAPH2 (Figure 2, Supplementary Table S4).…”

Section: Primary Ovarian Insufficiencymentioning

confidence: 99%

Formins in Human Disease

Labat-de-Hoz

Alonso

2021

Cells

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Almost 25 years have passed since a mutation of a formin gene, DIAPH1, was identified as being responsible for a human inherited disorder: a form of sensorineural hearing loss. Since then, our knowledge of the links between formins and disease has deepened considerably. Mutations of DIAPH1 and six other formin genes (DAAM2, DIAPH2, DIAPH3, FMN2, INF2 and FHOD3) have been identified as the genetic cause of a variety of inherited human disorders, including intellectual disability, renal disease, peripheral neuropathy, thrombocytopenia, primary ovarian insufficiency, hearing loss and cardiomyopathy. In addition, alterations in formin genes have been associated with a variety of pathological conditions, including developmental defects affecting the heart, nervous system and kidney, aging-related diseases, and cancer. This review summarizes the most recent discoveries about the involvement of formin alterations in monogenic disorders and other human pathological conditions, especially cancer, with which they have been associated. In vitro results and experiments in modified animal models are discussed. Finally, we outline the directions for future research in this field.

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Section: Primary Ovarian Insufficiencymentioning

confidence: 99%

Formins in Human Disease

Labat-de-Hoz

Alonso

2021

Cells

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“…POI manifestation may vary among individuals, presenting either with severe forms, such as absent pubertal development and primary amenorrhea, or milder forms with early post-pubertal onset with the disappearance of menstrual cycles (secondary amenorrhea) and defective folliculogenesis (Genesio et al 2015). It is generally characterized by elevated gonadotropin levels, hypoestrogenism, and amenorrhea, showing menopausal levels of folliclestimulating hormone (FSH), estradiol, and anti-mullerian hormone (AMH) (Visser et al 2012).…”

Section: Premature Ovarian Insufficiencymentioning

confidence: 99%

“…Similarly, Moysés-Oliveira et al determined the breakpoint of three patients with X-autosome translocations and POI, all of them with X chromosome breakpoint at POI2, but with no gene disruptions capable of explaining their ovarian dysgenesis (Moyses-Oliveira et al 2015). Genesio et al described one patient with a balanced translocation between Xq21 (POI2 region) and 1q41, presenting short stature and POI in whom no gene disruptions were identified but gene expression alterations of ovarian related genes were observed (Genesio et al 2015).…”

Section: Gene Disruption Hypothesismentioning

confidence: 99%

Genetics of premature ovarian insufficiency and the association with X-autosome translocations

2020

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Premature ovarian insufficiency (POI) is the cessation of menstruation before the age of 40 and can result from different etiologies, including genetic, autoimmune, and iatrogenic. Among genetic causes, single-gene mutations and cytogenetic alterations, such as X-chromosome aneuploidies and chromosome rearrangements, can be associated with POI. In this review, we summarize the genetic factors linked to POI and list the main candidate genes. We discuss the association of these genes with the ovarian development, the functional consequences of different mutational mechanisms and biological processes that are frequently disrupted during POI pathogenesis. Additionally, we focus on the high prevalence of X-autosome translocations involving the critical regions in Xq, known as POI1 and POI2, and deeply discuss the main hypotheses proposed to explain this association. Although the incorrect pairing of chromosomes during meiosis could lead to oocyte apoptosis, the reason for the prevalence of X-chromosome breakpoints at specific regions remains unclear. In most cases, studies on genes disrupted by balanced structural rearrangements cannot explain the ovarian failure. Thus, the position effect has emerged as a putative explanation among genetic mechanisms since translocations possibly result in changes in overall chromatin topology due to chromosome repositioning. Given the tremendous impact of POI on women’s quality of life, we highlight the value of investigations on the interplay between ovarian function and gene regulation to deepen our understanding of the molecular mechanisms related to this disease, with the ultimate goal of improving patients’ care and assistance.

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“…Translocated genome segments can activate chromosome position effects that may disturb gene expression either by altering the number or location of regulatory elements or by changing the architectural landscape of a gene or a genic cluster [34][35][36]. In the present case, the Xp22.33p22.31 translocated segment does not include the X-inactivation center (XIC).…”

Section: Discussionmentioning

confidence: 89%

Unbalanced X;9 translocation in an infertile male with de novo duplication Xp22.31p22.33

Roumelioti

Louizou²,

Karras

et al. 2019

J Assist Reprod Genet

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Purpose Male carriers of an X-autosome translocation are generally infertile, regardless of the position of the breakpoint on the X chromosome while the pathogenicity of Xp22.3 subtelomeric duplications is under debate. To shed light into this controversy, we present a rare case, of an azoospermic male with no other significant clinical findings, in whom classical cytogenetics revealed additional unbalanced chromosomal material, at the telomere of the long arm of one homolog of chromosome 9. Methods In peripheral blood specimens of the index case and his parents, we performed GBanding, Inverted-DAPI Banding, AgNOR staining, Telomere specific Fluorescence in Situ Hybridization (FISH), Molecular karyotyping by Multi-color FISH, whole genome SNP microarrays, sub-telomeric MLPA, and transcription analysis of the expression of KAL1 gene by RT-PCR. Results Multi-color FISH revealed an unbalanced translocation involving the short arm of chromosome X. SNP microarray analysis combined to classical cytogenetics and MLPA demonstrated a de novo 8.796 Mb duplication of Xp22.31-p22.33. Compared to three control specimens, the patient presented significantly elevated expression levels of KAL1 mRNA in peripheral blood, suggesting transcriptional functionality of the duplicated segment. Conclusions The duplicated segment contains the pseudo-autosomal region PAR1 and more than 30 genes including SHOX, ARSE, STS, KAL1, and FAM9A and is not listed as polymorphic. Our data advocate that duplications of the Xp22.3 region may not be associated with a clinical consequence.

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Short stature and primary ovarian insufficiency possibly due to chromosomal position effect in a balanced X;1 translocation

Cited by 13 publications

References 31 publications

Formins in Human Disease

Formins in Human Disease

Genetics of premature ovarian insufficiency and the association with X-autosome translocations

Unbalanced X;9 translocation in an infertile male with de novo duplication Xp22.31p22.33

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