DYT1 gene mutations lead to early-onset dystonia that begins with focal limb onset and spreads to other body regions within 5 years, with typical sparing of the oromandibular muscles. In the present study, we describe two patients with an unusual presentation of the disease.
- MeSH
- dítě MeSH
- dospělí MeSH
- dystonia musculorum deformans komplikace genetika patofyziologie terapie MeSH
- lidé MeSH
- tortikolis etiologie genetika patofyziologie terapie MeSH
- Check Tag
- dítě MeSH
- dospělí MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- dopisy MeSH
- kazuistiky MeSH
- práce podpořená grantem MeSH
Cells with DNA repair defects have increased genomic instability and are more likely to acquire secondary mutations that bring about cellular transformation. We describe the frequency and spectrum of somatic mutations involving several tumor suppressor genes in the rectal carcinoma of a 13-year-old girl harboring biallelic, germline mutations in the DNA mismatch repair gene PMS2. Apart from microsatellite instability, the tumor DNA contained a number of C:G→T:A or G:C→A:T transitions in CpG dinucleotides, which often result through spontaneous deamination of cytosine or 5-methylcytosine. Four DNA glycosylases, UNG2, SMUG1, MBD4 and TDG, are involved in the repair of these deamination events. We identified a heterozygous missense mutation in TDG, which was associated with TDG protein loss in the tumor. The CpGs mutated in this patient's tumor are generally methylated in normal colonic mucosa. Thus, it is highly likely that loss of TDG contributed to the supermutator phenotype and that most of the point mutations were caused by deamination of 5-methylcytosine to thymine, which remained uncorrected owing to the TDG deficiency. This case provides the first in vivo evidence of the key role of TDG in protecting the human genome against the deleterious effects of 5-methylcytosine deamination.
- MeSH
- adenosintrifosfatasy nedostatek genetika MeSH
- DNA vazebné proteiny nedostatek genetika MeSH
- enzymy opravy DNA nedostatek genetika MeSH
- fenotyp MeSH
- heterozygot MeSH
- homozygot MeSH
- lidé MeSH
- mladiství MeSH
- molekulární sekvence - údaje MeSH
- nádory rekta genetika metabolismus MeSH
- sekvence aminokyselin MeSH
- thymin-DNA-glykosylasa genetika metabolismus MeSH
- zárodečné mutace MeSH
- Check Tag
- lidé MeSH
- mladiství MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- kazuistiky MeSH
- práce podpořená grantem MeSH
- MeSH
- genetické markery MeSH
- lidé MeSH
- příznaky a symptomy MeSH
- syndrom bazocelulárního névu diagnóza etiologie terapie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- abstrakty MeSH
- Publikační typ
- abstrakt z konference MeSH
- MeSH
- feochromocytom genetika MeSH
- lidé MeSH
- von Hippelova-Lindauova nemoc genetika MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- kazuistiky MeSH
