Recently, biallelic variants in the SORD gene were identified as causal for axonal hereditary neuropathy (HN). We ascertained the spectrum and frequency of SORD variants among a large cohort of Czech patients with unknown cause of HN. Exome sequencing data were analysed for SORD (58 patients). The prevalent c.757del variant was tested with fragment analysis (931 patients). Sanger sequencing in additional 70 patients was done. PCR primers were designed to amplify the SORD gene with the exclusion of the pseudogene SORD2P. Sequence differences between gene and pseudogene were identified and frequencies of SNPs were calculated. Eighteen patients from 16 unrelated families with biallelic variants in the SORD gene were found and the c.757del was present in all patients on at least one allele. Three novel, probably pathogenic, variants were detected, always in a heterozygous state in combination with the c.757del on the second allele. Patients presented with a slowly progressive axonal HN. Almost all patients had moderate pes cavus deformity. SORD neuropathy is frequent in Czech patients and the third most common cause of autosomal recessive HN. The c.757del is highly prevalent. Specific amplification of the SORD gene with the exclusion of the pseudogene is essential for a precise molecular diagnostics.
- MeSH
- dospělí MeSH
- hereditární motorické a senzitivní neuropatie * diagnóza epidemiologie genetika MeSH
- kohortové studie MeSH
- lidé středního věku MeSH
- lidé MeSH
- mutace MeSH
- sekvenování exomu MeSH
- senioři MeSH
- sorbitoldehydrogenasa genetika MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Geografické názvy
- Česká republika MeSH
Rats were subjected to 4 h continuous and intermittent exposure to vinyl chloride (VC) at the time-weighted average concentration of 50,000 mg/m3. Prior to exposure, half of the animals obtained water, whereas the other half 0.1% sodium phenobarbital (PB) solution for seven consecutive days. The studies were focussed on: body weight, liver weight, activity of enzymes in the blood serum, activity of glutathione S-transferase in the liver cytoplasmatic and microsomal fraction, content of free non-protein sulfhydryl groups (NPSH) in the liver and urinary excretion of thiodiglycolic acid (TDGA). VC exposure, both continuous and intermittent, resulted in a decrease of body weight, NPSH depletion in the liver and TDGA urinary excretion. PB effects were manifested by the persistent decrease in rats' body weight, increase in the liver weight, increase in the cytoplasmatic activity of glutathione S-transferase in the liver and increase in TDGA urinary excretion. With none of the tested parameters, except TDGA, statistically significant differences between the continuous and intermittent VC exposure at the same time-weighted average concentration of 50,000 mg/m3, were found. TDGA urinary excretion was higher in rats poisoned in continuous exposure, as compared to the intermittent one.
- MeSH
- alanintransaminasa analýza MeSH
- alkalická fosfatasa analýza MeSH
- aspartátaminotransferasy analýza MeSH
- časové faktory MeSH
- fenobarbital škodlivé účinky MeSH
- glutathiontransferasa analýza MeSH
- jaterní mikrozomy analýza enzymologie MeSH
- játra účinky léků metabolismus MeSH
- krysa rodu rattus MeSH
- L-laktátdehydrogenasa analýza MeSH
- sorbitoldehydrogenasa analýza MeSH
- tělesná hmotnost účinky léků MeSH
- thioglykoláty analýza moč MeSH
- velikost orgánu účinky léků MeSH
- vinylchlorid škodlivé účinky MeSH
- vinylové sloučeniny škodlivé účinky MeSH
- vystavení vlivu životního prostředí MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- srovnávací studie MeSH
- MeSH
- laktátdehydrogenasy krev MeSH
- lipidy krev MeSH
- malátdehydrogenasa krev MeSH
- nemoci jater etiologie MeSH
- polychlorované bifenyly aplikace a dávkování krev toxicita MeSH
- potkani Wistar MeSH
- sorbitoldehydrogenasa krev MeSH
- vztah mezi dávkou a účinkem léčiva MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- MeSH
- chlorid uhličitý * aplikace a dávkování metabolismus škodlivé účinky MeSH
- experimenty na zvířatech MeSH
- fosfatasy fyziologie účinky léků MeSH
- hepatocyty účinky léků MeSH
- játra * MeSH
- krysa rodu rattus MeSH
- ornithinkarbamoyltransferasa fyziologie účinky léků MeSH
- sorbitoldehydrogenasa fyziologie účinky léků MeSH
- transaminasy fyziologie účinky léků MeSH
- Check Tag
- krysa rodu rattus MeSH
- Publikační typ
- klinická studie MeSH
- MeSH
- chlorid uhličitý toxicita MeSH
- lidé MeSH
- nemoci jater MeSH
- oxidoreduktasy krev MeSH
- sorbitoldehydrogenasa MeSH
- Check Tag
- lidé MeSH
