ArticleMolecular diagnosis : a journal devoted to the understanding of human disease through the clinical application of molecular biology2005
Skewed X inactivation of the normal allele in fully mutated female carriers determines the levels of FMRP in blood and the fragile X phenotype.
Article in Molecular diagnosis : a journal devoted to the understanding of human disease through the clinical application of molecular biology, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
13 citing papers in PubMed, 24 citations in OpenAlex.
- Article
- Neurobehavioral Outcomes Relate to Activation Ratio in Female Carriers of Fragile X Syndrome Full Mutation: Two Pediatric Case Studies.International journal of molecular sciences · 2025Article
- Advances in the study of ARR3 in myopia.Frontiers in cell and developmental biology · 2025Review
- Fragile sites, chromosomal lesions, tandem repeats, and disease.Frontiers in genetics · 2022Review
- The Impact of X-Chromosome Inactivation on Phenotypic Expression of X-Linked Neurodevelopmental Disorders.Brain sciences · 2021Review
- FMRP regulates the subcellular distribution of cortical dendritic spine density in a non-cell-autonomous manner.Neurobiology of disease · 2021Article
- High-functioning autism spectrum disorder and fragile X syndrome: report of two affected sisters.Molecular autism · 2012Article
- A nonsense mutation in FMR1 causing fragile X syndrome.European journal of human genetics : EJHG · 2011Article
- Paternally biased X inactivation in mouse neonatal brain.Genome biology · 2010Article
- May anomalous X chromosome methylation be responsible for the spontaneous abortion of a male foetus?Journal of genetics · 2008Article
- Highly skewed inactivation of the wild-type X-chromosome in asymptomatic female carriers of spinal and bulbar muscular atrophy (Kennedy's disease).Journal of neurology · 2008Article
- Presynaptic FMR1 genotype influences the degree of synaptic connectivity in a mosaic mouse model of fragile X syndrome.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2007Article
- X-chromosome inactivation patterns in females with Prader-Willi syndrome.American journal of medical genetics. Part A · 2007Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe variable phenotype in female carriers of a full mutation is explained in part by non-random X-chromosome inactivation. The molecular diagnosis of fragile X syndrome is based on the resolution of the number of CGG triplet repeats and the methylation status of a critical CpG in the fragile X mental retardation gene (FMR1) promoter. Neighboring CpGs in the FMR1 promoter are supposed to be equally methylated or unmethylated.
methodSouthern blot analysis was performed with double digestion, either with EcoRI/EagI or with HindIII/SacII. The EagI restriction site was studied by sequencing. The fragile X encoded protein (FMRP) was detected in white blood cells by Western blot. The fragile X phenotype was evaluated by specific clinical examinations.
resultsWithin one family we found three female carriers of a full mutation and a different degree of methylation of the normal allele that correlated with the levels of FMRP in blood and the fragile X phenotype. Complete methylation at the EagI CpG target (but partially methylated SacII CpG site) was associated with extremely skewed X inactivation (confirmed by analysis of the methylation status at the PGK locus), undetectable FMRP in blood, and a male-like phenotype.
conclusionsIn fully mutated female carriers the methylation status at the EagI restriction site correlates with the levels of FMRP in blood and the fragile X phenotype. Neighboring CpG sequences in the FMR1 promoter can be differentially methylated, which should be taken into consideration for molecular diagnosis.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.