A fragile X case with an amplification/deletion mosaic pattern

Arocena, Dolores Garcia; Diego, Yolanda de; Oostra, Ben A.; Willemsen, Rob; Rodriguez, Maria-Mirta

doi:10.1007/s004390051052

Cited by 19 publications

(13 citation statements)

References 7 publications

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“…However, several studies have described mutations involving deletion of the FMR1 CGG repeat region and adjacent sequences (Garcia Arocena et al, 2000;Fan et al, 2005). It is possible that a not-insubstantial number of FXS cases might result from the deletion mechanism that was seen in our study, but it is difficult to make an accurate determination at this time since most of the techniques used in screening surveys evaluate only the gene region containing the CGG repeats (McConkie-Rosell et al, 2005).…”

Section: Discussionmentioning

confidence: 78%

Short Communication Screening for fragile X syndrome in males from specialized institutions in the northeast region of Brazil

Viveiros¹,

Santos²,

Santos³

et al. 2015

Genet. Mol. Res.

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ABSTRACT. The objective of this study was to perform a study of fragile X syndrome (FXS) in São Luís, Maranhão, in males residing in five specialized institutions. Two hundred thirty-eight males with intellectual disability of unknown etiology participated in this study. Blood samples were processed and stored until DNA extraction. Screening for FMR1 gene mutations was performed using non-isotopic polymerase chain reaction amplification and DNA sequencing using an ABI Prism 3130 automated sequencer. Two individuals (0.84%) were positive for FMR1 mutations. One had a mutation due to expansion of the CGG M.T.M. Viveiros et al. 6898©FUNPEC-RP www.funpecrp.com.br Genetics and Molecular Research 14 (2): 6897-6905 (2015) repeat beyond normal levels and the other had a deletion in exon 1 of the FMR1 gene, which was confirmed by sequencing. Both probands were over 18 years old, which demonstrates the late diagnosis of the condition in these individuals and reinforces the need to implement effective programs for early diagnosis of FXS in the state of Maranhão. We found that FXS might be transmitted in the families of the two individuals bearing the mutation, and that it is important to understand the mutation dynamics to provide better counseling to the family members of these two individuals.

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Section: Discussionmentioning

confidence: 78%

Short Communication Screening for fragile X syndrome in males from specialized institutions in the northeast region of Brazil

Viveiros¹,

Santos²,

Santos³

et al. 2015

Genet. Mol. Res.

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“…DNA polymerase slippage or slipped strand mis-pairing (SSM) may be leading to the reduction of the CGG length. The contraction process generally occurs in GC-rich repetitive sequences possibly by transient detachment of newly synthesized strand and mis-pairing during DNA replication because of the repetitive nature of the CGG stretch [44,45]. It was demonstrated that CpG methylation and SSM may facilitate the formation of deletion events.…”

Section: Discussionmentioning

confidence: 99%

Contraction of a Maternal Fragile X Mental Retardation 1 Premutation Allele

et al. 2015

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Fragile X syndrome (FXS) is mainly caused by an expansion of a cytosine-guanine-guanine (CGG) trinucleotide repeat (greater than 200) in the 5' untranslated region of the fragile X mental retardation 1 (FMR1) gene resulting in gene silencing, methylation, and absence of FMRP. FXS involves a wide spectrum of phenotypes including intellectual disabilities, autism spectrum disorder (ASD), maladaptive behaviors or symptoms, social anxiety, mood disorders and physical features. Carriers of premutation alleles (55 -200 CGG repeats) can manifest with neurodevelopmental phenotypes and are at risk for the neurodegenerative fragile X-associated tremor/ataxia syndrome (FX-TAS) and about 20% of women with a premutation develop fragile Xassociated primary ovarian insufficiency (FXPOI). These phenotypes are believed to be caused by a distinct molecular mechanism involving increased FMR1 mRNA production and toxicity. Premutation alleles are unstable and depending on the CGG length and the presence of AGG interruptions have the potential to expand to larger premutation or full mutation alleles during transmission from mothers to their children. The contraction of a CGG repeat allele, although rare, has been observed. Here, we report the case of a three-generation family, who was identified as part of a pilot study of newborn screening for FXS. Specifically, the maternal grandmother carried a premutation allele (109 CGG repeats), which contracted to an intermediate size allele (52 CGG repeats) in her son, the father of a newborn girl (proband). This allele expanded to a premutation allele of 59 CGG repeats in the proband newborn. A premutation allele of 61 CGG repeats was detected in the proband's sister who demonstrated social phobia but normal cognition. The proband newborn showed some fragile X associated physical stigmata but normal cognition. Intriguingly, all FMR1 CGG expanded allele showed no AGG interruptions. This case shows a remarkable instability of premutation alleles throughout the three generations likely arising from different mechanisms.

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“…Approximately 20-40% of the male patients display such a mosaic DNA pattern. In addition, FMRP expression studies in males with somatic mosaicism for the FM and a partial deletion of the FMR1 gene have been also described [De Graaff et al, 1996;García Arocena et al, 2000]. Males with mosaic pattern (FM + PM) have been shown in some reports to have higher mental function than males with the FM [Merenstein et al, 1996].…”

Section: Mosaic Malesmentioning

confidence: 93%

FMRP detection assay for the diagnosis of the fragile X syndrome

Willemsen

Oostra

2000

Am. J. Med. Genet.

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Fragile X syndrome is almost always caused by the absence or deficit of the FMR1 protein (FMRP). Diagnostic methods include polymerase chain reaction and Southern blotting, which are performed on DNA isolated from peripheral leukocytes. Recently, different immunocytochemical tests have been described to identify patients with fragile X syndrome, based on the detection of FMRP in cells by a monoclonal antibody. This review aims to provide an update on the different antibody methods for prenatal and postnatal diagnosis of the fragile X syndrome.

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A fragile X case with an amplification/deletion mosaic pattern

Cited by 19 publications

References 7 publications

Short Communication Screening for fragile X syndrome in males from specialized institutions in the northeast region of Brazil

Short Communication Screening for fragile X syndrome in males from specialized institutions in the northeast region of Brazil

Contraction of a Maternal Fragile X Mental Retardation 1 Premutation Allele

FMRP detection assay for the diagnosis of the fragile X syndrome

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