Newborn Screening for Fragile X Syndrome

Tassone, Flora

doi:10.1001/jamaneurol.2013.4808

Cited by 44 publications

(48 citation statements)

References 16 publications

(28 reference statements)

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“…However, recent reports from large screening studies that demonstrated the technical feasibility of widespread testing, the benefits of genetic counseling, and advances in treatment, may change this situation. In the case of FXS, identification of carriers not only enables counseling about the risk of having a child with FXS, but may also inform about personal health risks (Tassone, 2014). Tassone et al (2008) reported a PCR-based screening method for FXS detection.…”

Section: Fxsmentioning

confidence: 99%

“…New targeted treatments will continue to develop and multiple family members with clinical involvement identified through neonatal diagnosis and familial cascade testing will also benefit from early treatment and long-term follow-up (Tassone, 2014). It is vital for pediatricians and other clinicians to be familiar with the medical problems related to FXS so that affected patients may receive proper diagnosis and treatment.…”

Section: Clinical Utility Of the Diagnostic Testmentioning

confidence: 99%

See 1 more Smart Citation

Genetic tests for low- and middle-income countries: a literature review

Maltese¹,

Poplavskaia

Malyutkina

et al. 2017

Genet. Mol. Res.

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ABSTRACT. The aim of this review is to describe a series of ten genetic diseases with Mendelian inheritance pattern in people of lowor middle-income countries, which can be easily identified with simple and affordable methods. Recent information shows that although genetic diseases account for more than 10% of infant mortality in such countries, testing, counseling, and treatment of genetic diseases is not a priority. The selection criteria for the genetic tests that are discussed in this review are: i) the frequency of the genetic disease in the general population, ii) the cost and ease of execution, and iii) the report of validated methods in the literature for the diagnosis of these diseases. The goal is to promote diagnosis of genetic diseases at low-cost and with relative ease, thereby enabling appropriate treatments, reducing mortality, and preventing genetic diseases in high-risk families.

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Section: Fxsmentioning

confidence: 99%

Section: Clinical Utility Of the Diagnostic Testmentioning

confidence: 99%

Genetic tests for low- and middle-income countries: a literature review

Maltese¹,

Poplavskaia

Malyutkina

et al. 2017

Genet. Mol. Res.

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show abstract

“…Such ubiquitous testing would reduce the timeto-diagnosis from years to weeks, and enable early intervention services to be used as soon as possible (21 ). Early intervention can mitigate the symptoms of FXS by improving development through various therapies (22 ).…”

Section: Clinical Applicationsmentioning

confidence: 99%

Group Testing Approach for Trinucleotide Repeat Expansion Disorder Screening

Kaseniit¹,

Theilmann²,

Robertson³

et al. 2016

Clinical Chemistry

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BACKGROUND Fragile X syndrome (FXS, OMIM #300624) is an X-linked condition caused by trinucleotide repeat expansions in the 5′ UTR (untranslated region) of the fragile X mental retardation 1 (FMR1) gene. FXS testing is commonly performed in expanded carrier screening and has been proposed for inclusion in newborn screening. However, because pathogenic alleles are long and have low complexity (>200 CGG repeats), FXS is currently tested by a single-plex electrophoresis-resolved PCR assay rather than multiplexed approaches like next-generation sequencing or mass spectrometry. In this work, we sought an experimental design based on nonadaptive group testing that could accurately and reliably identify the size of abnormally expanded FMR1 alleles of males and females. METHODS We developed a new group testing scheme named StairCase (SC) that was designed to the constraints of the FXS testing problem, and compared its performance to existing group testing schemes by simulation. We experimentally evaluated SC's performance on 210 samples from the Coriell Institute biorepositories using pooled PCR followed by capillary electrophoresis on 3 replicates of each of 3 pooling layouts differing by the mapping of samples to pools. RESULTS The SC pooled PCR approach demonstrated perfect classification of samples by clinical category (normal, intermediate, premutation, or full mutation) for 90 positives and 1800 negatives, with a batch of 210 samples requiring only 21 assays. CONCLUSIONS Group testing based on SC is an implementable approach to trinucleotide repeat expansion disorder testing that offers ≥10-fold reduction in assay costs over current single-plex methods.

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“…1 It is most frequently caused by hyperexpansion and hypermethylation of a polymorphic CGG trinucleotide repeat in the 5ʹ untranslated region of Fragile X Mental Retardation 1 (FMR1) gene on chromosome Xq27.3, resulting in transcriptional silencing of the gene. 2 Affected males typically have more severe phenotypes than females, including autism, intellectual and developmental disability, social anxiety, attention deficit hyperactivity, and other physical malformations.…”

Section: Introductionmentioning

confidence: 99%

Identification of microsatellite markers <1 Mb from the FMR1 CGG repeat and development of a single-tube tetradecaplex PCR panel of highly polymorphic markers for preimplantation genetic diagnosis of fragile X syndrome

Chen

Zhao

Lee

et al. 2016

Genetics in Medicine

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Purpose: To develop a single-tube polymerase chain reaction (PCR) panel of highly polymorphic markers for preimplantation genetic diagnosis (PGD) of fragile X syndrome (FXS).Methods: An in silico search was performed to identify all markers within 1 Mb flanking the FMR1 gene. Selected markers were optimized into a single-tube PCR panel and their polymorphism indices were determined from 272 female samples from three populations. The single-tube assay was also validated on 30 single cells to evaluate its applicability to FXS PGD.Results: Thirteen markers with potentially high polymorphism information content (PIC) and heterozygosity values were selected and optimized into a single-tube PCR panel together with AMELX/Y for gender determination. Analysis of 272 female samples confirmed the high polymorphism (PIC > 0.5) of most markers, with expected and observed heterozygosities ranging from 0.31 to 0.87. More than 99% of individuals were heterozygous for at least three markers, with 95.8% of individuals heterozygous for at least two markers on either side of the FMR1 CGG repeat. Conclusion:The tetradecaplex marker assay can be performed directly on single cells or after whole-genome amplification, thus supporting its use in FXS PGD either as a standalone linkage-based assay or as a complement to FMR1 mutation detection.

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Newborn Screening for Fragile X Syndrome

Cited by 44 publications

References 16 publications

Genetic tests for low- and middle-income countries: a literature review

Genetic tests for low- and middle-income countries: a literature review

Group Testing Approach for Trinucleotide Repeat Expansion Disorder Screening

Identification of microsatellite markers <1 Mb from the FMR1 CGG repeat and development of a single-tube tetradecaplex PCR panel of highly polymorphic markers for preimplantation genetic diagnosis of fragile X syndrome

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