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Carrier Screening For Inherited Genetic Conditions
Published in Vincenzo Berghella, Obstetric Evidence Based Guidelines, 2022
Whitney Bender, Lorraine Dugoff
Fragile X is an X-linked dominant disorder caused by expansion of a repetition of the CGG trinucleotide segment of the fragile X mental retardation 1 (FMR-1) gene. This gene is located on the X chromosome at Xq27.3.The full mutation (>200 repeats) results in the reduction or absence of fragile X mental retardation protein (FMRP), an RNA-binding protein involved in the maturation and elimination of synapses.
Genetic Counseling in Assisted Reproductive Technology
Published in Carlos Simón, Carmen Rubio, Handbook of Genetic Diagnostic Technologies in Reproductive Medicine, 2022
Expansion of the CGG triplet repeat in the FMR1 gene is responsible for fragile X syndrome. Women who carry a premutation in this gene do not have fragile X syndrome but can have a unique set of symptoms associated with a premutation, including primary ovarian insufficiency (POI). Women who carry the full mutation in this gene can have a diagnosis of fragile X syndrome, although, because of skewed X-inactivation and the presence of a fully functioning copy of the FMR1 gene on their other X chromosome, may manifest a milder form of the disease than males who inherit a full mutation. Clinical trials report an incidence of the FMR1 premutation in as many as 14% to 20% of women with familial POI and 2% to 5% of women with sporadic POI (Torrealday et al., 2017).
Degenerative Diseases of the Nervous System
Published in Philip B. Gorelick, Fernando D. Testai, Graeme J. Hankey, Joanna M. Wardlaw, Hankey's Clinical Neurology, 2020
James A. Mastrianni, Elizabeth A. Harris
The FMR1 gene in premutation carriers is transcribed efficiently and there is near-normal expression of the fragile X mental retardation protein, FMRP. However, there is a five- to eightfold increase in FMR1 mRNA levels.47
A bibliometric analysis of primary ovarian insufficiency from 2010 to 2020
Published in Climacteric, 2022
Z.-H. Deng, H.-J. Tan, L. Wang, P.-P. Long, D. Guo, R.-P. Quan, M.-H. Zeng, H.-W. Deng, H.-M. Xiao
Mutation in the FMR1 gene is associated with Fragile X syndrome, in which patients are more likely to suffer from POI. Turner syndrome is a rare condition in women that is associated with either complete or partial loss of one X chromosome. Typical clinical manifestations include ovarian dysgenesis, hypogonadotropic hypogonadism and infertility [20]. In addition to cancer patients, fertility preservation techniques may also be used in patients with Turner syndrome and Fragile X syndrome. Unfortunately, most of the data on fertility preservation available in the literature concern cancer patients while patients with syndromic POI present a particular complexity due to other co-presence symptoms. Fertility preservation in these patients should be treated accurately and individually [21].
Therapeutic potential of GABAA receptor subunit expression abnormalities in fragile X syndrome
Published in Expert Review of Precision Medicine and Drug Development, 2022
Mathijs B. van der Lei, R. Frank Kooy
Our review substantiates that specific subunits of the GABAA receptor are affected in a brain region and age-dependent manner in Fmr1 KO mice. Most studies have investigated the mRNA and protein expression of the GABAA receptors in the cortex, hippocampus, and cerebellum in juvenile and/or adult Fmr1 KO mice. Based on summarizing these outcomes we conclude that there is consensus for a decreased mRNA expression of the α1-α3, β1, δ and γ1-2 subunits in the cortex, α2, β1 and δ subunits in the hippocampus, and for the α1-α3 subunits in the cerebellum of juvenile Fmr1 KO mice, as shown in Figure 1. Adult Fmr1 KO mice showed a decrease in mRNA expression for the α1, α3, α4, δ and γ1-2 subunits in the cortex , and the β2 and δ subunits in the hippocampus. A decrease in mRNA expression was not found for any of the GABAA receptor subunits in the cerebellum of adult Fmr1 KO mice.
Premutations in the FMR1 gene in Serbian patients with undetermined tremor, ataxia and parkinsonism
Published in Neurological Research, 2021
Milica Pešić, Nataša Dragašević Mišković, Ana Marjanović, Valerija Dobričić, Nela Maksimović, Marina Svetel, Dijana Perović, Ivana Novaković, Sanja Cirković, Iva Stanković, Vladimir Kostić
The main finding of our study was that among older patients with unexplained degenerative ataxia and action tremor, with or without parkinsonism and/or cognitive impairment, 2% were the FMR1 gene premutation carriers (55–200 CGG repeats), suggesting a diagnosis of FXTAS. This estimate was in accordance with previously published data. Among patients with ataxia, the frequency of the FMR1 premutations varied from 0% to 5% [14–23]: in the late-onset ataxia up to 2.2% [24], and in male ataxic patients with SCAs negative genetics 5% [25]. Such premutations were present in 0% to 4% of patients clinically diagnosed as MSA [26–28], and in 0% to 1% of patients with parkinsonism [29–31]. No premutation carriers were identified in patients with ET [32] or FA [15]. However, it has been still probable that many of these patients were missed, possibly since only a small number of patients truly had an insight into their own condition [33]. For instance, patients with FXTAS have rarely been referred to genetic testing for ataxia, and only 17% of them were labelled as ataxic before it was revealed that they actually had FXTAS [5,33]. Unlike many other inherited ataxias, patients with FXTAS have a broader spectrum of clinical manifestations [34]. For patients with parkinsonism and bradykinesia, associated with cerebellar ataxia, or postural instability accompanied with intention tremor, it is more likely to have FMR1 premutation than, for those without these combinations of motor symptoms [35].