Fully mutated and gray-zoneFRAXA alleles in Brazilian mentally retarded boys

Haddad, Luciana A.; Aguiar, Marcos José Burle de; Costa, Silvia Souza da; Mingroni‐Netto, Regina Célia; Vianna‐Morgante, Angela Maria; Pena, Sérgio D.J.

doi:10.1002/(sici)1096-8628(19990528)84:3<198::aid-ajmg5>3.0.co;2-w

Cited by 27 publications

(17 citation statements)

References 16 publications

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“…Gray zone alleles were detected among patients as well as in the control group with frequencies of 3.03 and 2.70%, respectively (P = 0.38, Fisher exact test). Gray zone allele frequencies in these two groups were also similar to those previously reported (Haddad et al, 1999;Garcia Arocena et al, 2004;Toft et al, 2005). No premutation alleles in Figure 1.…”

Section: Resultssupporting

confidence: 89%

Frequency of FMR1 premutation in individuals with ataxia and/or tremorand/or parkinsonism

Reis

Ferreira²,

Gomes³

et al. 2008

Genet. Mol. Res.

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ABSTRACT.A late onset neurological syndrome in carriers of premutation in FMR1 gene was recently described. The condition was named fragile-X-associated tremor/ataxia syndrome (FXTAS) and includes intentional tremor, cerebellar ataxia, parkinsonism, and cognitive deficit. We ascertained the contribution of FMR1 premutation to the phenotypes ataxia, tremor and/or parkinsonism. Sixty-six men over 45 years old presenting these symptoms, isolated or combined, were tested. Also, 74 normal men, randomly chosen in the population, formed the control group. In the patient group, no premutation carrier was found, which is in agreement with other observed frequencies reported elsewhere (0-5% variation). 75Frequency of FMR1 in ataxia, tremor or parkinsonism No significant differences were found when comparing gray zone allele frequencies among target and control groups. The FXTAS contribution in patients with phenotypic manifestations of FXTAS was 15/748 (2%). The presence of gray zone alleles is not correlated with FXTAS occurrence.

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Section: Resultssupporting

confidence: 89%

Frequency of FMR1 premutation in individuals with ataxia and/or tremorand/or parkinsonism

Reis

Ferreira²,

Gomes³

et al. 2008

Genet. Mol. Res.

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“…Some studies 10,11 have reported an excess of these alleles in ID cohorts, suggesting a possible phenotypic effect in the intellectual functioning. Others, including the present study, have failed to replicate these results (listed in Table 3).…”

Section: Discussionmentioning

confidence: 99%

“…A study of patients with ID in the Brazilian population 10 reported a higher frequency of IA alleles in ID boys (6.3%) than in normal male controls (2.4%). In a similar study in a Southern England cohort of ID patients, 11 an unexpected excess of IA alleles of 4% was found compared with 2.4% for controls.…”

Section: Introductionmentioning

confidence: 97%

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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“…We used DNA from eight patients with fragile X syndrome, all confirmed by Southern blot analysis: five of these were ascertained in a screening study of mentally retarded boys in Brazil (Haddad et al, 1999), two were patients diagnosed at GENE and the other (NA06852) was obtained from the Coriell Mutant Cell Repository (Camden, NJ, USA). DNA samples from 42 normal controls were obtained from paternity testing cases at GENE.…”

Section: Patientsmentioning

confidence: 99%

“…The second drawback resulted from the "failure-toamplify" characteristic of the test that thus could not provide a definitive diagnosis of fragile X syndrome. Although not quite suitable for medical diagnosis, the PCR test proved to be a useful tool for fragile X syndrome screening in populations of mentally retarded males (Haddad et al, 1999).…”

Section: Introductionmentioning

confidence: 99%

Diagnosis of the fragile X syndrome in males using methylation-specific PCR of the FMRI locus

Pena¹,

Sturzeneker²

1999

Genet. Mol. Biol.

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We have developed a non-isotopic technique based on methylation-specific PCR (MSP) of the FMR1 promoter for the identification of fragile X full mutations among men. DNA samples were first treated with sodium bisulfite to convert unmethylated, but not methylated, cytosines to uracil, followed by PCR amplification with oligonucleotide primers specific for methylated versus unmethylated DNA. We designed two primer pairs: one produced a 142-bp fragment from the bisulfite-treated methylated CpG island, while the other generated an 84-bp product from the treated non-methylated promoter. In normal males only the 84-bp fragment was seen, while the diagnosis of FRAXA was doubly indicated by the appearance of a 142-bp product together with absence or weak visualization of the 84-bp band. As an indispensable internal control for the efficiency of the sodium bisulfite treatment, we used a primer pair specific for the imprinted maternal methylated version of the CpG island of the SNRPN gene on human chromosome 15. Using the methylation-specific PCR we identified with 100% sensitivity and accuracy eight previously diagnosed FRAXA male patients mixed with 42 normal controls. Because of its simplicity and high efficiency, methylation-specific PCR may become the method of choice for the diagnosis of the fragile X syndrome in mentally retarded males.

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Fully mutated and gray-zoneFRAXA alleles in Brazilian mentally retarded boys

Cited by 27 publications

References 16 publications

Frequency of FMR1 premutation in individuals with ataxia and/or tremorand/or parkinsonism

Frequency of FMR1 premutation in individuals with ataxia and/or tremorand/or parkinsonism

Intermediate FMR1 alleles and cognitive and/or behavioural phenotypes

Diagnosis of the fragile X syndrome in males using methylation-specific PCR of the FMRI locus

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