Abstract
BackgroundPremature ovarian failure (POF) has repeatedly been associated to X-chromosome deletions. FMR1 gene premutation allele's carrier women have an increased risk for POF. We intent to determine the cause of POF in a 29 year old female, evaluating both of these situations.MethodsConcomitant analysis of FMR1 gene CGG repeat number and karyotype revealed an X-chromosome terminal deletion. Fluorescence in situ further characterized the breakpoint. A methylation assay for FMR1 gene allowed to determine its methylation status, and hence, the methylation status of the normal X-chromosome.ResultsWe report a POF patient with a 46,X,del(X)(q26) karyotype and with skewed X-chromosome inactivation of the structural abnormal X-chromosome.ConclusionsDespite the hemizygosity of FMR1 gene, the patient does not present Fragile X syndrome features, since the normal X-chromosome is not subject to methylation. The described deletion supports the hypothesis that haploinsufficiency of X-linked genes can be on the basis of POF, and special attention should be paid to X-linked genes in region Xq28 since they escape inactivation and might have a role in this disorder. A full clinical and cytogenetic characterization of all POF cases is important to highlight a pattern and help to understand which genes are crucial for normal ovarian development.
Highlights
Premature ovarian failure (POF) has repeatedly been associated to X-chromosome deletions
Premature ovarian failure (POF) is an early ovarian dysfunction characterized by the cessation of menses before the age of 40 years [1,2] that affects 1% of women [3]
One of the genes known to be associated with POF is FMR1 (Fragile X mental retardation), located at Xq27.3 and responsible for Fragile X Syndrome (FXS)
Summary
Premature ovarian failure (POF) has repeatedly been associated to X-chromosome deletions. One of the genes known to be associated with POF is FMR1 (Fragile X mental retardation), located at Xq27.3 and responsible for Fragile X Syndrome (FXS) It is a form of X-linked mental retardation caused by the expansion of an instable CGG repeat in the 5′ untranslated region of the gene [1,10]. The syndrome occurs when the number of the repeats exceeds 200, being denominated as full mutation alleles This is responsible for hypermethylation and gene inactivation, leading to absence of FMRP (Fragile X mental retardation protein) and, causing mental retardation [11]. Since full mutation carriers do not have an increased risk for ovarian dysfunction, the molecular mechanism underlying the association between POF and premutation alleles, still unravelled, should not be related to the absence or reduction of FMRP [12]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
