FMR1 gene expansion, large deletion of Xp, and skewed X-inactivation in a girl with mental retardation and autism
Jazyk angličtina Země Spojené státy americké Médium print
Typ dokumentu kazuistiky, časopisecké články, práce podpořená grantem
PubMed
20425835
DOI
10.1002/ajmg.a.33352
Knihovny.cz E-zdroje
- MeSH
- autistická porucha komplikace genetika MeSH
- chromozomální delece * MeSH
- dítě MeSH
- dospělí MeSH
- expanze trinukleotidových repetic genetika MeSH
- genetické lokusy genetika MeSH
- inaktivace chromozomu X genetika MeSH
- karyotypizace MeSH
- kojenec MeSH
- lidé středního věku MeSH
- lidé MeSH
- lidské chromozomy X genetika MeSH
- mentální retardace komplikace genetika MeSH
- metylace DNA genetika MeSH
- protein FMRP genetika MeSH
- rodiče MeSH
- Southernův blotting MeSH
- těhotenství MeSH
- zlomy chromozomů MeSH
- Check Tag
- dítě MeSH
- dospělí MeSH
- kojenec MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- kazuistiky MeSH
- práce podpořená grantem MeSH
- Názvy látek
- protein FMRP MeSH
We describe a girl with mild facial anomalies, mild mental retardation, and atypical autism with a remarkable behavioral phenotype of persistent anger, aggression, and dysphoria. The occurrence of late-onset tremor and premature ovarian failure in the maternal branch of the family pointed to a possible defect in the FMR1 gene. Indeed, the patient carried a full FMR1 mutation. Unexpectedly, both alleles of the gene were almost completely methylated. Cytogenetic examination of the patient revealed in addition a large de novo deletion in band Xp22 on one of her X chromosomes. The deletion was fine mapped using oligonucleotide array CGH, and its breakpoints were localized using sequencing. The size of the deletion was about 17.4 Mb, and it contained more than 90 protein-coding genes. Microsatellite analysis indicated paternal origin of the aberrant chromosome. The large rearrangement was the most probable cause of the X-inactivation skewing, thus explaining the methylation of not only the expanded (maternal) but also the normal (paternal) FMR1 alleles. This pattern of skewed X-inactivation was confirmed using the analysis of methylation at the AR locus. The relatively mild phenotype of the patient resulted most likely from unmasking of the FMR1 defect. Although the deleted region contained many important genes, the phenotypic contribution of the rearranged X chromosome was probably limited by its almost complete inactivation. However, reduced dose of several genes escaping X-inactivation might also play a role in the phenotype of the patient.
Citace poskytuje Crossref.org