Finding<i>FMR1</i>mosaicism in Fragile X syndrome

Gonçalves, Thaís Fernandez; Santos, J. M.; Gonçalves, Andressa Pereira; Tassone, Flora; Ribeiro, Márcia Gonçalves; Kahn, Evelyn; Boy, Raquel; Pimentel, Márcia Mattos Gonçalves; Santos-Rebouças, Cíntia Barros

doi:10.1586/14737159.2016.1135739

Cited by 20 publications

(17 citation statements)

References 33 publications

(39 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Generally, a combination of methods might be required to characterize these different facets of the FMR1 expansion mutation [11,93]. …”

Section: Diagnostic Tools For Characterizing the Multiple Moleculamentioning

confidence: 99%

Molecular Correlates and Recent Advancements in the Diagnosis and Screening of FMR1-Related Disorders

Rajan‐Babu

Chong

2016

Genes

View full text Add to dashboard Cite

Fragile X syndrome (FXS) is the most common monogenic cause of intellectual disability and autism. Molecular diagnostic testing of FXS and related disorders (fragile X-associated primary ovarian insufficiency (FXPOI) and fragile X-associated tremor/ataxia syndrome (FXTAS)) relies on a combination of polymerase chain reaction (PCR) and Southern blot (SB) for the fragile X mental retardation 1 (FMR1) CGG-repeat expansion and methylation analyses. Recent advancements in PCR-based technologies have enabled the characterization of the complete spectrum of CGG-repeat mutation, with or without methylation assessment, and, as a result, have reduced our reliance on the labor- and time-intensive SB, which is the gold standard FXS diagnostic test. The newer and more robust triplet-primed PCR or TP-PCR assays allow the mapping of AGG interruptions and enable the predictive analysis of the risks of unstable CGG expansion during mother-to-child transmission. In this review, we have summarized the correlation between several molecular elements, including CGG-repeat size, methylation, mosaicism and skewed X-chromosome inactivation, and the extent of clinical involvement in patients with FMR1-related disorders, and reviewed key developments in PCR-based methodologies for the molecular diagnosis of FXS, FXTAS and FXPOI, and large-scale (CGG)n expansion screening in newborns, women of reproductive age and high-risk populations.

show abstract

“…Generally, a combination of methods might be required to characterize these different facets of the FMR1 expansion mutation [11,93]. …”

Section: Diagnostic Tools For Characterizing the Multiple Moleculamentioning

confidence: 99%

Molecular Correlates and Recent Advancements in the Diagnosis and Screening of FMR1-Related Disorders

Rajan‐Babu

Chong

2016

Genes

View full text Add to dashboard Cite

show abstract

“…En la literatura, se reporta entre un 12 % y un 41 % de mosaicismo (premutación y mutación completa) en los varones con SFX, 12 que concuerda con lo hallado en nuestro trabajo (el 18,5 %).…”

Section: Discussionunclassified

Fragilidad del X y otras entidades asociadas al gen FMR1: estudio de 28 familias afectadas

2019

Arch Argent Pediat

View full text Add to dashboard Cite

Presentación de casos clínicos RESUMEN El síndrome de fragilidad del cromosoma X es la causa de discapacidad intelectual heredable más frecuente. Asociado a trastornos del espectro autista en un tercio de los pacientes, afecta, con mayor prevalencia, a los varones. Se debe a una expansión de trinucleótidos CGG (citosina, guanina, guanina), llamada mutación completa en el locus Xq27.3 del gen FMR1, que conduce a la hipermetilación en el promotor del gen y reduce los niveles de expresión de FMRP, una proteína implicada en la maduración y plasticidad sináptica. Una expansión menor de CGG es la causa de insuficiencia ovárica primaria y del síndrome de temblor/ataxia asociado a X frágil, caracterizado por ataxia cerebelosa progresiva, de inicio tardío, y temblor de intención. En el presente estudio de serie de casos, se analiza la segregación de mutaciones del gen FMR1 en diferentes familias y la variabilidad de expresión clínica que llevó a la consulta genética. Palabras clave: síndrome del cromosoma X frágil, FMR1, discapacidad intelectual, insuficiencia ovárica primaria, síndrome de temblor/ataxia.

show abstract

“…Published studies indicated that FoSTeS/MMBIR is a mitotic event rather than a meiotic one, e.g. somatic mutations associated with the PMP22 and FMR1 genes [ 16 , 31 ]. Therefore, c.532_574del in the ATP7B gene could have occurred through a single FoSTeS/MMBIR event during the mitotic cell division of somatic cells in grandparents or ancestors of the proband (Fig.…”

Section: Discussionmentioning

confidence: 99%

Identification and characterization of a novel 43-bp deletion mutation of the ATP7B gene in a Chinese patient with Wilson’s disease: a case report

Liu

Cheng

et al. 2018

BMC Med Genet

View full text Add to dashboard Cite

BackgroundWilson’s disease (WD) is an autosomal recessive disorder characterized by copper accumulation. ATP7B gene mutations lead to ATP7B protein dysfunction, which in turn causes Wilson’s disease.Case presentationWe describe a male case of Wilson’s disease diagnosed at 10 years after routine biochemical test that showed low serum ceruloplasmin levels and Kayser–Fleischer rings in both corneas. Analysis of the ATP7B gene revealed compound heterozygous mutations in the proband, including the reported c.3517G > A mutation and a novel c.532_574del mutation. The c.532_574del mutation covered a 43-bp region in exon 2, and resulted in a frameshift mutation (p.Leu178PhefsX10). By base sequence analysis, two microhomologies (TCTCA) were observed on both deletion breakpoints in the ATP7B gene. Meanwhile, the presence of some sequence motifs associated with DNA breakage near the deletion region promoted DNA strand break.ConclusionsBy comparison, a replication-based mechanism named fork stalling and template switching/ microhomology-mediated break-induced replication (FoSTeS/MMBIR) was used to explain the formation of this novel deletion mutation.Electronic supplementary materialThe online version of this article (10.1186/s12881-018-0567-z) contains supplementary material, which is available to authorized users.

show abstract

FindingFMR1mosaicism in Fragile X syndrome

Cited by 20 publications

References 33 publications

Molecular Correlates and Recent Advancements in the Diagnosis and Screening of FMR1-Related Disorders

Molecular Correlates and Recent Advancements in the Diagnosis and Screening of FMR1-Related Disorders

Fragilidad del X y otras entidades asociadas al gen FMR1: estudio de 28 familias afectadas

Identification and characterization of a novel 43-bp deletion mutation of the ATP7B gene in a Chinese patient with Wilson’s disease: a case report

Contact Info

Product

Resources

About