- Publikační typ
- abstrakt z konference MeSH
- Publikační typ
- abstrakt z konference MeSH
- Publikační typ
- abstrakt z konference MeSH
- MeSH
- financování organizované MeSH
- Publikační typ
- abstrakty MeSH
Smith-Lemli-Opitz syndrome (SLOS) is an autosomal recessive metabolic disorder. SLOS is caused by the mutations in the gene for 3beta-hydroxysterol Delta(7) reductase (DHCR7; EC 1.3.1.21), which maps to chromosome 11q12-13. DHCR7 catalyses the final step in cholesterol biosynthesis-the reduction of 7-dehydrocholesterol to cholesterol. Clinical severity ranges from mild dysmorphism to severe congenital malformation and intrauterine lethality. Pregnant women are offered a biochemical screening test for Down syndrome in the second trimester, where the suspicion for SLOS could be registered, when the unconjugated estriol (uE3) level appears low. A group of 456 fetuses with a high risk for SLOS were examined by DNA analysis. We confirmed SLOS in 5 fetuses and 11 fetuses were carriers. One novel mutation (p.G30A) was detected. The most frequently found mutations, c.964-1G > C and p.W151X, are also the most severe ones. At least one of these mutations was detected in each fetus with SLOS. This suggests that the biochemical screening of pregnant women probably uncovers mainly more severely affected fetuses. We confirmed SLOS also in two patients whose prenatal screening was negative. Both of them had nonsense mutation on one allele. It stands to reason that some modifying factors may play a role in the reduction of the uE3 level in the mother's serum.
- MeSH
- alely MeSH
- biochemie MeSH
- financování organizované MeSH
- genotyp MeSH
- heterozygot MeSH
- komplikace těhotenství MeSH
- lidé MeSH
- mutace MeSH
- mutační analýza DNA MeSH
- nesmyslný kodon MeSH
- plošný screening metody MeSH
- riziko MeSH
- Smithův-Lemliho-Opitzův syndrom diagnóza genetika MeSH
- těhotenství MeSH
- Check Tag
- lidé MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- Geografické názvy
- Česká republika MeSH
Syndrom fragilního X chromozomu je X vázané dědičné onemocnění projevující se mentální retardací u postižených mužů a lehčí mentální dysfunkcí u postižených žen. Většina nemocných má také poruchy chování včetně hyperaktivity a autismu. Na molekulární úrovni jsou známy 2 rozdílné typy syndromu fragilního X chromozomu: FRAXA a FRAXE. Článek pojednává o klinické a molekulárně-genetické analýze rodiny s výskytem syndromu fragilního X chromozomu typu FRAXE, která zatím v naší literatuře nebyla popsána. U probanda s psychomotorickou retardací byl molekulární analýzou vyloučen syndrom typu FRAXA. Kombinací polymerázové řetězové reakce (PCR) a Southernova blottingu byla zavedena metoda pro detekci syndromu typu FRAXE. Popsaná technika umožňuje určit zvětšení a přibližnou velikost (CCG)n repetice v 5' oblasti FMR2 genu. Bylo zjištěno, že matka probanda je nositelkou mutantní FRAXE alely, kterou předala svému synovi. V souladu s dříve publikovanými údaji byla potvrzena nestabilita (CCG)n repetitivní oblasti FMR2 genu v průběhu přenosu z jedné generace do druhé jak ve smyslu její expanze, tak také její kontrakce. Sdělení poukazuje na důležitost DNA analýzy nejen FMR1 genu (typ FRAXA), ale i FMR2 genu (typ FRAXE) u pacientů s mentální retardací s podezřením na syndrom fragilního X chromozomu.
Fragile X syndrome is X linked inherited disease which manifests with mental retardation at affected males and mild mental dysfunction at affected females. Majority of patients háve also behavioral problems including hyperactivity and autism. There are two different types of fragile X syndrome on the molecular level: FRAXA and FRAXE. Present article deal with clinical and molecular genetics analysis of affected family for the FRAXE type of fragile X syndrome that has not been described in the Czech literatuře yet. First, the FRAXA type of syndrome was excluded by molecular analysis at the proband with psychomotor retardation. Consecutively, a method for detection of the FRAXE type of syndrome was established by combination of polymerase chain reaction (PCR) and Southern blotting. Described technique allows to determine an expansion and approximate size of (CCG)n repeat at the 5' end of the FMR2 gene. It was found that mother of the proband is a carrier of the mutant FRAXE allele which passed to her son. In agreement with previously published results, it was confirmed that the (CCG)n repeat at the FMR2 gene is unstable when passed through one generation to the next. Both, the expansion and the contraction of the (CCG)n repeat was observed at studied family. Our report indicates that not only DNA analysis of FMR1 gene (FRAXA type) but also DNA analysis of FMR2 gene (FRAXE type) is important at patients with mental retardation that are suspected for fragile X syndrome.
