Fragile X syndrome: Diagnostic and carrier testing

Sherman, Stephanie L.; Pletcher, Beth A.; Driscoll, Deborah A.

doi:10.1097/01.gim.0000182468.22666.dd

Cited by 250 publications

(208 citation statements)

References 17 publications

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“…If indicated, Southern blot was performed by hybridizing the probe StB12.3 to EcoRI-and EagI digested DNA. The sensitivity of both the PCR and Southern blot analyses was 99 % [16][17][18][19].…”

Section: Laboratory Analysesmentioning

confidence: 99%

Evidence of an age-related correlation of ovarian reserve and FMR1 repeat number among women with “normal” CGG repeat status

Gustin

Ding

Desai

et al. 2015

J Assist Reprod Genet

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Purpose The objective of this analysis is to examine the relationship between Fragile X Mental Retardation 1 gene (FMR1) cytosine-guanine-guanine (CGG) repeat number and ovarian reserve, with a particular focus exclusively on the range of CGG repeat number below the premutation (PM) range (<55 CGG repeats). Methods Our study included female patients who underwent assessment of FMR1 CGG repeat number and serum antiMullerian hormone (AMH) in 2009-2014. To examine the association between FMR1 repeat number and serum AMH, we created three summary measures of CGG repeat number for the two alleles-BSum,^BMax,^and BGap^(absolute difference). Using multivariable regression models, controlling for age, we then analyzed the impact of these summary measures on AMH.Results A total of 566 patients were included in our study. Using multivariable regression models, we found that the relationship between CGG repeat number and AMH differed depending on age. Specifically, in younger women, AMH increased by 7-8 % (Sum p<0.01, Max p=0.04) for every 1 unit increase in CGG repeat number. In contrast, starting at age 40, there was a 3 to 5 % decline in AMH for every 1 unit increase in CGG repeat number (Sum p<0.01, Max p=0.04). Conclusions This is the first study to report a statistically significant correlation of ovarian reserve and CGG repeat number in women with <55 CGG repeats. Although these women are generally considered to have a normal phenotype, our data suggest that increasing CGG repeat number within this normal range is associated with a more rapid decline in ovarian reserve.

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Section: Laboratory Analysesmentioning

confidence: 99%

Evidence of an age-related correlation of ovarian reserve and FMR1 repeat number among women with “normal” CGG repeat status

Gustin

Ding

Desai

et al. 2015

J Assist Reprod Genet

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“…The need for appropriate education and genetic counseling has been emphasized as has the importance of research exploring psychosocial impacts of such screening (Finucane et al 2012;Sherman et al 2005). Research indicates that population screening for FXS is generally perceived favorably by families and healthcare providers (Acharya and Ross 2009;Archibald et al 2013;Ryynanen et al 1999;Skinner et al 2003) as well as individuals offered screening in research contexts (Anido et al 2005(Anido et al , 2007Archibald et al 2009;Fanos et al 2006;Metcalfe et al 2008;Sherman et al 2005), and there appears to be a preference for screening offered before pregnancy (Acharya and Ross 2009;Archibald et al 2013;Skinner et al 2003). As carrier screening approaches have varied, there is no clear consensus on how best to deliver population-based carrier screening for FXS.…”

Section: Introductionmentioning

confidence: 99%

“It gives them more options”: preferences for preconception genetic carrier screening for fragile X syndrome in primary healthcare

et al. 2016

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This study aims to explore stakeholder views about offering population-based genetic carrier screening for fragile X syndrome. A qualitative study using interviews and focus groups with stakeholders was undertaken to allow for an indepth exploration of views and perceptions about practicalities of, and strategies for, offering carrier screening for fragile X syndrome to the general population in healthcare settings. A total of 188 stakeholders took part including healthcare providers (n = 81), relatives of people with fragile X syndrome (n = 29), and members of the general community (n = 78). The importance of raising community awareness about screening and providing appropriate support for carriers was emphasized. There was a preference for preconception carrier screening and for providing people with the opportunity to make an informed decision about screening. Primary care was highlighted as a setting which would ensure screening is accessible; however, challenges of offering screening in primary care were identified including time to discuss screening, knowledge about the test and possible outcomes, and the health professionals' approach to offering screening. With the increasing availability of genetic carrier tests, it is essential that research now focuses on evaluating approaches for the delivery of carrier screening programs. Primary healthcare is perceived as an appropriate setting through which to access the target population, and raising awareness is essential to making genetic screening more accessible to the general community.

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“…Both the American College of Obstetrics and Gynecology (ACOG) and the American College of Medical Genetics and Genomic (ACMGG) have classified the limits of the CGG alleles of the FMR1 gene into normal Capsule This paper reviews current evidence regarding the possible conditions that may present in women with premutation-sized repeats beyond FXPOI. repeats), intermediate (45-54 repeats), premutation (55-200 repeats), and full mutation (>200 repeats) [2][3][4]. If the number of repeats goes above 200, hypermethylation of the repeat sequence and an adjacent CpG island occurs, which leads to silencing of the gene and therefore an absence of fragile X mental retardation protein (FMRP) [5,6].…”

Section: Introductionmentioning

confidence: 99%

“…In addition, women may request screening regardless of family history [4]. Polymerase chain reaction (PCR) and Southern blot analysis are used in testing to determine the individual's genotype [3].…”

Section: Introductionmentioning

confidence: 99%

Fragile X premutation in women: recognizing the health challenges beyond primary ovarian insufficiency

Hoyos

Thakur

2016

J Assist Reprod Genet

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Fragile X premutation carriers have 55-200 CGG repeats in the 5' untranslated region of the FMR1 gene. Women with this premutation face many physical and emotional challenges in their life. Approximately 20% of these women will develop fragile X-associated primary ovarian insufficiency (FXPOI). In addition, they suffer from increased rates of menstrual dysfunction, diminished ovarian reserve, reduction in age of menopause, infertility, dizygotic twinning, and risk of having an offspring with a premutation or full mutation. Consequent chronic hypoestrogenism may result in impaired bone health and increased cardiovascular risk. Neuropsychiatric issues include risk of developing fragile X-associated tremor/ataxia syndrome, neuropathy, musculoskeletal problems, increased prevalence of anxiety, depression, and sleep disturbances independent of the stress of raising an offspring with fragile X syndrome and higher risk of postpartum depression. Some studies have reported a higher prevalence of thyroid abnormalities and hypertension in these women. Reproductive health providers play an important role in the health supervision of women with fragile X premutation. Awareness of these risks and correlation of the various manifestations could help in early diagnosis and coordination of care and services for these women and their families. This paper reviews current evidence regarding the possible conditions that may present in women with premutation-sized repeats beyond FXPOI.

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Fragile X syndrome: Diagnostic and carrier testing

Cited by 250 publications

References 17 publications

Evidence of an age-related correlation of ovarian reserve and FMR1 repeat number among women with “normal” CGG repeat status

Evidence of an age-related correlation of ovarian reserve and FMR1 repeat number among women with “normal” CGG repeat status

“It gives them more options”: preferences for preconception genetic carrier screening for fragile X syndrome in primary healthcare

Fragile X premutation in women: recognizing the health challenges beyond primary ovarian insufficiency

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