Linking the FMR1 alleles with small CGG expansions with neurodevelopmental disorders: Preliminary data suggest an involvement of epigenetic mechanisms

Loesch, Danuta Z.; Godler, David E.; Khaniani, Mahmoud Shekari; Gould, Emma; Gehling, Freya; Dissanayake, Cheryl; Burgess, Trent; Tassone, Flora; Huggins, Richard; Slater, Howard R.; Choo, KH Andy

doi:10.1002/ajmg.a.32990

Cited by 26 publications

(33 citation statements)

References 29 publications

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“…Two studies reported a significant increase of intermediate alleles in POF populations (15,16). Previously, we showed that intermediate alleles are associated with parkinsonism (11), and also reported that epigenetic components might be involved in the toxicity of excessive mRNA in small size alleles (17). Our preliminary results showed that PM and IM alleles may be attributed to neurodevelopmental conditions (17).…”

Section: Introductionsupporting

confidence: 59%

“…So far, clinical involvement of intermediate size alleles has been proved in POF, but not much evidence has been presented for neurodegenerative and neurodevelopmental disorders. The association of small CGG repeat expansion FMR1 alleles with parkinsonism and autistic phenotype in Australian population has been presented (17,25,26). We continued our research in other ethnic groups in order to confirm pervious findings.…”

Section: Discussionmentioning

confidence: 61%

“…Previously, we showed that intermediate alleles are associated with parkinsonism (11), and also reported that epigenetic components might be involved in the toxicity of excessive mRNA in small size alleles (17). Our preliminary results showed that PM and IM alleles may be attributed to neurodevelopmental conditions (17). Therefore, current literature suggests autism and small size alleles might overlap.…”

Section: Introductionmentioning

confidence: 51%

“…Genomic DNA was extracted from whole blood based on salting out method (17). Pureness and amount of the isolated DNA samples were measured by spectrophotometry.…”

Section: Molecular Analysismentioning

confidence: 99%

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Autistic Phenotype of Permutation and Intermediate Alleles of FMR1 Gene

et al. 2017

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Section: Introductionsupporting

confidence: 59%

Section: Discussionmentioning

confidence: 61%

Section: Introductionmentioning

confidence: 51%

“…Genomic DNA was extracted from whole blood based on salting out method (17). Pureness and amount of the isolated DNA samples were measured by spectrophotometry.…”

Section: Molecular Analysismentioning

confidence: 99%

See 2 more Smart Citations

Autistic Phenotype of Permutation and Intermediate Alleles of FMR1 Gene

et al. 2017

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“…A high frequency of IA has also been associated with an increased risk of behavioural phenotypes. Specifically, Loesch et al 23 found an association of IA with an increased risk of autistic behaviour. Nevertheless, considering the small sample size analysed (n¼42), this affirmation required studies with larger cohorts.…”

Section: Discussionmentioning

confidence: 99%

Intermediate FMR1 alleles and cognitive and/or behavioural phenotypes

et al. 2011

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During the last few years, several studies have reported an excess of intermediate FMR1 alleles in patients with cognitive and/or behavioural phenotypes. Here, we report the frequency of intermediate alleles (IAs) in three pathologies, intellectual disabilities (IDs), attention-deficit/hyperactivity disorder and autism, from different Spanish regions. We found 142 IAs among 9015 patients with ID (1.6%), 4 among the 415 ADHD patients (0.96%) and 4 among the 300 autistic patients (1.3%), similar to the frequency reported in our control population. No evidence was found of an excess of IA at the FRAXA locus in any of the study populations, although geographical variability was detected. Moreover, the analysis of 100 transmissions of IAs showed that 95% of these alleles were stable. Only 3% expanded within the same range and 2% expanded to a full mutation in two generations. No evidence of an association between IAs and behavioural or cognitive phenotypes was found, suggesting that IAs are not clearly implicated in these pathologies.

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“It's about having the choice”: Stakeholder perceptions of population‐based genetic carrier screening for fragile X syndrome

Archibald

Hickerton

Jaques

et al. 2012

American J of Med Genetics Pt A

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This project explored, the views of key stakeholders regarding population-based genetic carrier screening for fragile X syndrome (FXS). Interviews and focus groups were conducted with healthcare providers, relatives of individuals with FXS and members of the general population. Data were transcribed verbatim and coded into themes. 188 individuals took part in this study. Perceived benefits of carrier screening included: learning the risk of having a child with FXS; learning the risk of fragile X-associated primary ovarian insufficiency; and the opportunity for carriers to access reproductive options. Concerns included: the emotional impact of screening and receiving a carrier result; the predictive testing nature of the carrier test with respect to fragile X-associated tremor/ataxia syndrome; potential confusion created by receiving an intermediate result; and implications of genetic screening for society. Overall, population-based genetic carrier screening was perceived to be acceptable provided it is optional and offered at an appropriate stage of life. With the support of the participants to promote individual choice by offering a population-based carrier screening program for FXS, it is essential to carefully consider how screening might be offered in order to ensure broad accessibility and facilitation of decision-making.

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Linking the FMR1 alleles with small CGG expansions with neurodevelopmental disorders: Preliminary data suggest an involvement of epigenetic mechanisms

Cited by 26 publications

References 29 publications

Autistic Phenotype of Permutation and Intermediate Alleles of FMR1 Gene

Autistic Phenotype of Permutation and Intermediate Alleles of FMR1 Gene

Intermediate FMR1 alleles and cognitive and/or behavioural phenotypes

“It's about having the choice”: Stakeholder perceptions of population‐based genetic carrier screening for fragile X syndrome

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